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IEEE拒绝收录的138个会议列表-推荐下载

IEEE拒绝收录的138个会议列表2011-10-27 14:54:18| 分类：EI、ISTP检索国际 | 标签：ieee 收录 138 会议列表 |字号大中小订阅IEEE拒绝收录的138个会议列表138个会议名单如下:2010 2nd Asia-Pacific Conference on Information Processing (APCIP)2010 2nd International Asia Symposium on Intelligent Interaction and Affective Computing & 2010 2nd International onInnovation Management (ASIA-ICIM)2010 2nd International Conference on Future Computer and Communication (FCC) 2010 2nd International Conference on Information and Multimedia Technology (ICIMT)2010 2nd International Conference on Intellectual Technique in Industrial Practice (ITIP 2010)2010 2nd International Conference on Multimedia and Computational Intelligence (ICMCI)2010 2nd International Conference on Research Challenges in Computer Science (ICRCCS)2010 2nd International Symposium on Computer Network and Multimedia Technology (CNMT 2010)2010 3rd International Conference on Computational Intelligence and Industrial Application (PACIIA)2010 3rd International Conference on Environmental and Computer Science (ICECS) 2010 3rd International Conference on Machine Vision (ICMV)2010 3rd International Conference on Power Electronics and Intelligent Transportation System (PEITS)2010 4th International Conference on Intelligent Information Technology Application (IITA)2010 6th International Conference on MEMS, NANO, and Smart Systems (ICMENS) 2010 First International Conference on Cellular, Molecular Biology, Biophysics and Bioengineering (CMBB)2010 IIS 2nd International Conference on Signal Processing, Robotics and Automation (ICSRA 2010)2010 International Asia Conference on Optical Instrument and Measurement (ACPIM)2010 International Conference on Bio-Inspired Systems and Signal Processing (ICBSSP)2010 International Conference on Biology, Environment and Chemistry (ICBEC) 2010 International Conference on Broadcast Technology and MultimediaCommunication (BTMC)2010 International Conference on Circuit and Signal Processing (ICCSP)2010 International Conference on Communication and Vehicular Technology (ICCVT)2010 International Conference on Computational Intelligence and Vehicular System (CIVS)2010 International Conference on Computer and Computational Intelligence (ICCCI) 2010 International Conference on Computer and Software Modeling (ICCSM)2010 International Conference on Computer Science and Sports Engineering (CSSE) 2010 International Conference on Computer-Aided Manufacturing and Design (CMD)2010 International Conference on Construction and Project Management (ICCPM) 2010 International Conference on Digital Enterprise and Digital Manufacturing (DEDM)2010 International Conference on E-business, Management and Economics (ICEME) 2010 International Conference on Economics, Business and Management (ICEBM) 2010 International Conference on Electrical Engineering and Automatic Control (ICEEAC)2010 International Conference on Embedded Systems and Microprocessors (ICESM) 2010 International Conference on Engineering Education and Educational Technology (EEET)2010 International Conference on Future Biomedical Information Engineering (FBIE) 2010 International Conference on Future Computer, Control and Communication (FCCC)2010 International Conference on Future Industrial Engineering and Application (ICFIEA)2010 International Conference on Future Information Technology (ICFIT)2010 International Conference on Future Information Technology and Computing (FITC)2010 International Conference on Graphic and Image Processing (ICGIP)2010 International Conference on Information and Finance (ICIF)2010 International Conference on Information Security and Artificial Intelligence (ISAI)2010 International Conference on Intelligence and Information Technology (ICIIT) 2010 International Conference on Intelligent Network and Computing (ICINC)2010 International Conference on Management Science (ICMS)2010 International Conference on Management Science and Information Engineering (ICMSIE)2010 International Conference on Manufacturing Science and Technology (ICMST) 2010 International Conference on Measurement and Control Engineering (ICMCE) 2010 International Conference on Mechanical and Aerospace Engineering (ICMAE) 2010 International Conference on Mechanical Engineering, Robotics and Aerospace (ICMERA)2010 International Conference on Modeling, Simulation and Control (ICMSC 2010)2010 International Conference on Nano Science and Technology (ICNST)2010 International Conference on Nanotechnology and Biosensors (ICNB)2010 International Conference on Nuclear Energy and Engineering Technology (NEET)2010 International Conference on Physics Science and Technology (ICPST)2010 International Conference on Psychology, Psychological Sciences and Computer Science (PPSCS)2010 International Conference on Remote Sensing (ICRS)2010 International Conference on Semiconductor Laser and Photonics (ICSLP)2010 International Conference on Services Science, Management and Engineering (SSME)2010 International Conference on Signal and Information Processing (ICSIP)2010 International Conference on Software and Computing Technology (ICSCT) 2010 International Conference on Sport Medicine, Sport Science, and Computer Science (SMSSCS)2010 ISECS International Colloquium on Computing, Communication, Control, and Management (CCCM 2010)2010 Second International Conference on E-Learning, E-Business, Enterprise Information Systems, and E-Government(EEEE)2010 Second International Conference on Test and Measurement (ICMT)2010 Second International Seminar on Business and Information Management (ISBIM)2010 Third International Conference on Computer and Electrical Engineering (ICCEE)2010 Third International Conference on Education Technology and Training (ETT) 2010 Third International Symposium on Intelligent Ubiquitous Computing and Education (IUCE)2010 Third Pacific-Asia Conference on Web Mining and Web-Based Application (WMWA)2011 15th Global Chinese Conference on Computers in Education (GCCCE)2011 2nd Asia-Pacific Conference on Wearable Computing Systems (APWCS)2011 2nd International Conference on Biomedical Engineering and Computer Science (ICBECS)2011 2nd International Conference on Biotechnology and Food Science (ICBFS) 2011 2nd International Conference on Data Storage and Data Engineering (DSDE) 2011 2nd International Conference on Environmental Science and Technology (ICEST)2011 2nd International Conference on Financial Theory and Engineering (ICFTE) 2011 2nd International Conference on Mechanical, Industrial, and Manufacturing Technologies (MIMT)2011 2nd Intl Conf on Innovative Computing & Communication and 2010 Asia-Pacific Conf on Information Technology &Ocean Engineering, (CICC-ITOE)2011 2nd World Congress on Computer Science and Information Engineering (CSIE) 2011 3rd IEEE International Conference on Information Management and Engineering (ICIME)2011 3rd International Conference on Bioinformatics and Biomedical Technology (ICBBT 2011)2011 3rd International Conference on Computer and Automation Engineering (ICCAE)2011 3rd International Conference on Computer and Network Technology (ICCNT) 2011 3rd International Conference on Computer Design and Applications (ICCDA 2011)2011 3rd International Conference on Computer Modeling and Simulation (ICCMS) 2011 3rd International Conference on E-business and Information System Security (EBISS)2011 3rd International Conference on Machine Learning and Computing (ICMLC) 2011 3rd International Conference on Networks Security, Wireless Communications and Trusted Computing (NSWCTC)2011 3rd International Conference on Signal Acquisition and Processing (ICSAP) 2011 3rd International Workshop on Education Technology and Computer Science (ETCS)2011 4th IEEE International Conference on Computer Science and Information Technology (ICCSIT 2011)2011 IEEE International Conference on Information and Education Technology (ICIET)2011 IEEE International Conference on Smart Grid and Clean Energy Technologies (ICSGCE)2011 International Conference on Applied Physics and Mathematics (ICAPM 2011) 2011 International Conference on Bioinformatics and Computational Biology (ICBCB)2011 International Conference on Bioscience, Biochemistry and Bioinformatics (ICBBB)2011 International Conference on Communication and Electronics Information (ICCEI)2011 International Conference on Computer and Communication Devices (ICCCD) 2011 International Conference on Computer Applications and Network Security (ICCANS)2011 International Conference on Computers, Communications, Control and Automation (CCCA)2011 International Conference on Control, Robotics and Cybernetics (ICCRC)2011 International Conference on Data Engineering and Internet Technology (DEIT) 2011 International Conference on Database and Data Mining (ICDDM)2011 International Conference on Digital Convergence (ICDC)2011 International Conference on Economics and Finance Research (ICEFR)2011 International Conference on Economics, Business and Marketing Management (CEBMM)2011 International Conference on Economics, Trade and Development (ICETD) 2011 International Conference on Electrical Energy and Networks (ICEEN)2011 International Conference on Energy and Environment (ICEE)2011 International Conference on Engineering and Information Management (ICEIM) 2011 International Conference on Environment Science and Engineering (ICESE) 2011 International Conference on Environmental Science and Development (ICESD) 2011 International Conference on Future Environment and Energy (ICFEE 2011) 2011 International Conference on Fuzzy Systems and Neural Computing (FSNC) 2011 International Conference on Information and Computer Applications (ICICA) 2011 International Conference on Information and Computer Networks (ICICN) 2011 International Conference on Information and Industrial Electronics (ICIIE) 2011 International Conference on Information Engineering and Mechanical Engineering (IEME)2011 International Conference on Innovation and Information Management (ICIIM) 2011 International Conference on Intelligent Information Networks (ICIIN)2011 International Conference on Knowledge Discovery (ICKD)2011 International Conference on Life Science and Technology (ICLST)2011 International Conference on Manufacturing and Industrial Engineering (ICMIE) 2011 International Conference on Mechanical and Aerospace Engineering (ICMAE) 2011 International Conference on Medical Information and Bioengineering (ICMIB) 2011 International Conference on Network Communication and Computer (ICNCC) 2011 International Conference on Product Development and Renewable Energy Resources (ICPDRE)2011 International Conference on Security Science and Technology (ICSST)2011 International Conference on Social Science and Humanity (ICSSH)2011 International Conference on Solid-State and Integrated Circuit (ICSIC)2011 International Conference on System Design and Data Proceesing (ICSDDP) 2011 International Conference on System。

第六章表观遗传学

NIH-National Institutes of Health(美国)
Epigenetic changes have been associated with disease, but further progress requires the development of better methods to detect the modifications and a clearer understanding of factors that drive these changes. 192 million USD for 5 years ( 2008 to 2012)
获得性遗传（ Inheritance
of acquired characteristics）
Jean-Baptiste Lamarck
(1744-1829)
问题环境的作用能否改变个体的遗传特性，并传递给下一代?
这种被称为“拉马克学说”(Lamarckism) 的观点一直被正统的生物学家拒之门外。
AHEAD(人类表观基因组与疾病联合会）（Alliance for the Human Epigenome and Disease）计划.
The international AHEAD scientific committee will discuss the issue of the global collaborative efforts in light of the recent launch of NIH routemap Epigenetics program
effect variegation (PEV) —— 第一种表观遗
传学现象。 1942年，Waddington提出现代Epigenetics的

baltic oi 2010 day1 总结

baltic oi 2010 day1 总结Baltic IO 2010 Day 1 SummaryThe Baltic IO 2010 conference commenced with great enthusiasm and participation from experts in the field of Industrial Organization. The first day of the event was filled with insightful discussions, engaging presentations, and networking opportunities.The day began with a warm welcome from the conference organizers, followed by an introduction to the diverse range of topics to be discussed during the event. The attendees were then presented with the schedule for the day, featuring several highly anticipated presentations.The conference kicked off with a keynote address by Professor John Smith from the University of Economics. His speech focused on the current state of the industrial organization field and highlighted emerging trends and challenges faced by researchers and practitioners. Professor Smith's address set the tone for the rest of the day, inspiring participants to delve deeper into the topics at hand.This was followed by a series of parallel sessions that covered various aspects of industrial organization, including competition policy, market dynamics, and firm behavior. Each session featured high-quality research papers presented by esteemed scholars. The presentations were followed by detailed discussions, where participants had the opportunity to ask questions and provide their inputs.The lunch break provided an excellent opportunity for participants to network and interact with fellow researchers and industry professionals. The event had attracted a diverse group of attendees, ranging from academics to policymakers and business executives, leading to lively exchanges of ideas and experiences.After lunch, the conference continued with more parallel sessions, addressing topics such as innovation and technology, market structures, and regulatory frameworks. The presentations continued to impress, offering valuable insights into the challenges faced by various industries in today's rapidly changing business environment.To conclude the day, a panel discussion was held, focusing on the future perspectives of industrial organization. The panel consisted of experienced practitioners and scholars who shared their thoughts on the future direction of research and its potential impact on policy and business strategies.Overall, the first day of Baltic IO 2010 was a resounding success, with a wide range of topics discussed and valuable insights shared. The event provided a platform for researchers and industry professionals to connect, exchange ideas, and contribute to the advancement of the field of industrial organization.。

epigenetic修改对蛋白质表达的影响

epigenetic修改对蛋白质表达的影响Epigenetic Modifications and Their Impact on Protein ExpressionIntroduction:Epigenetic modifications refer to heritable changes in gene expression that do not involve alterations to the DNA sequence itself. These modifications can regulate gene activity and play a crucial role in various biological processes. In recent years, there has been increasing interest in understanding how epigenetic modifications influence protein expression. This article aims to explore the effects of epigenetic modifications on protein expression and discuss their significance in different cellular contexts.1. DNA Methylation:One of the most extensively studied epigenetic modifications is DNA methylation, which involves the addition of a methyl group to the DNA molecule. DNA methylation can act as a gene silencer by blocking the binding of transcription factors, thereby repressing gene expression. The presence of methyl groups on specific gene regions can lead to long-term suppression of protein production.2. Histone Modifications:Histone modifications refer to the post-translational modifications of histone proteins, which are responsible for packaging DNA into a compact structure called chromatin. Different types of histone modifications, such as acetylation, methylation, and phosphorylation, can either activate or suppress gene expression depending on the specific modification and itslocation on the histone tail. These modifications can directly influence the accessibility of DNA to transcriptional machinery, thereby impacting protein expression levels.3. Non-coding RNAs:In addition to DNA methylation and histone modifications, non-coding RNAs have emerged as key regulators of gene expression and protein production. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two main types of non-coding RNAs that can interact with messenger RNAs (mRNAs) to influence their stability and translation efficiency. By binding to specific mRNA sequences, miRNAs and lncRNAs can either enhance or inhibit protein expression, thus exerting control over cellular processes.4. Developmental Regulation:Epigenetic modifications are crucial for proper development and differentiation of cells. During embryogenesis, specific genes need to be activated or suppressed at precise time points and in specific cell types. Epigenetic modifications play a vital role in orchestrating these processes by regulating protein expression. For example, DNA methylation patterns can be inherited from parent cells during cell division, ensuring the transmission of specific gene expression profiles across generations.5. Disease Implications:Aberrant epigenetic modifications have been implicated in various diseases, including cancer, neurological disorders, and autoimmune conditions. In cancer, altered DNA methylation patterns and histonemodifications can lead to abnormal expression of oncogenes or tumor suppressor genes, promoting uncontrolled cell growth. Understanding the epigenetic drivers of these diseases can provide valuable insights for developing targeted therapies and biomarkers.Conclusion:Epigenetic modifications have a profound impact on protein expression and play a crucial role in various biological processes. By influencing gene activity, DNA methylation, histone modifications, and non-coding RNAs can fine-tune protein levels and regulate cellular functions. Further research into the mechanisms and functional consequences of epigenetic modifications will deepen our understanding of gene regulation and potentially lead to novel therapeutic interventions.。

Epigenetic Regulation of Development

Epigenetic Regulation of Development Epigenetic regulation of development is a complex process that involves the modification of gene expression without altering the DNA sequence. It plays a crucial role in various stages of development, including embryonic development, cell differentiation, and tissue-specific gene expression. Epigenetic modifications are heritable and reversible, making them an essential mechanism for regulating gene expression during development. In this essay, we will discuss the role of epigenetic regulation in development from different perspectives.From a biological perspective, epigenetic regulation is a fundamental mechanism that ensures the proper development of an organism. During embryonic development, cells undergo a series of epigenetic modifications that determine their fate and function. For example, DNA methylation, histone modification, and non-coding RNA regulation are essential epigenetic mechanisms that regulate gene expression during development. These modifications ensure that genes are expressed at the right time and in the right place, which is critical for proper development.From a medical perspective, epigenetic regulation plays a significant role in the development of various diseases. Epigenetic changes can alter gene expression and contribute to the development of cancer, neurological disorders, and other diseases. For example, aberrant DNA methylation patterns have been linked to the development of cancer. Understanding the epigenetic mechanisms that contribute to disease development can help in the development of new treatments and therapies.From an ethical perspective, epigenetic regulation raises ethical concerns about the manipulation of gene expression. Advances in epigenetic research have made it possible to manipulate gene expression and alter the development of an organism. This raises concerns about the potential misuse of this technology, such as the creation of designer babies. It is essential to consider the ethical implications of epigenetic research and ensure that it is used for the benefit of society.From a social perspective, epigenetic regulation has the potential to impact society in various ways. For example, epigenetic research can provide insights into the effects of environmental factors on gene expression and development. This can help in the development of public health policies and interventions that promote healthy development. Additionally, epigenetic research can help in the development of personalized medicine, which can lead to better health outcomes for individuals.From a personal perspective, epigenetic regulation is a fascinating area of research that has the potential to impact individuals' lives. Understanding the epigenetic mechanisms that regulate gene expression can provide insights into the development of diseases and potential treatments. Additionally, epigenetic research can help individuals make lifestyle choices that promote healthy development. For example, research has shown that environmental factors, such as diet and stress, can impact epigenetic modifications and alter gene expression. By understanding these mechanisms, individuals can make informed decisions about their health.In conclusion, epigenetic regulation plays a crucial role in development from various perspectives, including biological, medical, ethical, social, and personal. Understanding the epigenetic mechanisms that regulate gene expression can provide insights into the development of diseases and potential treatments. Additionally, epigenetic research can help in the development of public health policies and interventions that promote healthy development. However, it is essential to consider the ethical implications of epigenetic research and ensure that it is used for the benefit of society. Overall, epigenetic regulation is a fascinating area of research that has the potential to impact individuals' lives significantly.。

Epigenetics of sex determination and gonadogenesis--本科论文翻译

性别决定和性腺分化的表观遗传学原文来源：Francesc Piferrer. Epigenetics of sex determination and gonadogenesis[J]. Dev. Dyn.,2013,2424:.360-370译文正文：摘要表观遗传学通常被定义为对于不能用DNA序列改变解释的基因功能遗传性变化的研究。

基因表达调控的三大表观遗传机制包括DNA甲基化，组蛋白修饰以及非编码RNA。

表观遗传机制赋予了生物体结合基因组及环境中的信息修饰基因活性来产生特殊表型的能力。

在发育过程中，细胞通过基因表达的改变进行分化，增殖并维持个体生长。

作为保证物种的正常运转和延续的最重要发育过程之一，这对于性别决定和分化是关键性的。

本文对于表观遗传调控机制在植物、无脊椎动物及脊椎动物中如何促进它们的性别决定和生殖器官的形成所作的研究进行了总结。

进一步进展将通过整合多种方法进行，包括基因组学和新一代测序方法。

目的在于产生涉及不同层面的性别决定及性腺分化的表观遗传图。

表观遗传学也将有助于我们理解一些障碍性发育的病因。

它也可能在动物养殖场生产的生育控制中发挥重要作用，并将有助于我们认识环境与遗传对于处在全球变化的情况下敏感的物种性别决定的影响。

关键词：DNA甲基化；组蛋白修饰；非编码RNA；多梳/三胸；性发育障碍；性分化；生育控制；全球变化正文表观遗传学是生物学中一个非常令人兴奋的领域，当下正经历着惊人的发展。

表观遗传学的范围（Eccleston等，2007年）是辩论的主题，并因此提出了几个定义（Bird，2007年）。

这里，我将使用Russo等人提出的定义：表观遗传学是“有关引起可遗传的基因功能改变的有丝分裂和/或减数分裂的研究，这些变化无法以DNA序列改变来解释。

”在定义中的专业术语"遗传"一词已经产生了某些混淆，因为实际上它传递了两个不同的含义：这些变化不仅是在细胞有丝分裂过程中从一个细胞遗传给它的子细胞，还在配子形成过程中通过细胞的减数分裂遗传，继而能够将这些变化从父母传递到后代(Gilbert和Epel, 2009年)。

表观遗传与环境

REVIEW PAPEREnvironmental epigenetics:prospects for studying epigenetic mediation of exposure–response relationshipsVictoria K.Cortessis •Duncan C.Thomas •A.Joan Levine •Carrie V.Breton •Thomas M.Mack •Kimberly D.Siegmund •Robert W.Haile •Peter irdReceived:21February 2012/Accepted:7June 2012/Published online:28June 2012ÓThe Author(s)2012.This article is published with open access at Abstract Changes in epigenetic marks such as DNA methylation and histone acetylation are associated with a broad range of disease traits,including cancer,asthma,metabolic disorders,and various reproductive conditions.It seems plausible that changes in epigenetic state may be induced by environmental exposures such as malnutrition,tobacco smoke,air pollutants,metals,organic chemicals,other sources of oxidative stress,and the microbiome,particularly if the exposure occurs during key periods of development.Thus,epigenetic changes could represent an important pathway by which environmental factors inﬂu-ence disease risks,both within individuals and across generations.We discuss some of the challenges in studyingepigenetic mediation of pathogenesis and describe some unique opportunities for exploring these phenomena.Abbreviations ART Assisted reproductive technologies ASM Allele-speciﬁc DNA methylation ChIP Chromatin immunoprecipitation CIMP CpG island methylator phenotype CpG Cytosine-phosphate-guanine dinucleotide CRC Colorectal cancer DES Diethylstilbestrol feNO Fractional exhaled nitric oxide FFPE Formalin-ﬁxed parafﬁn-embedded HDAC Histone deacetylases iNOS Inducible nitric oxide synthase IUGR Intra-uterine growth restriction IVF In vitro fertilizationPBMCs Peripheral blood mononuclear cells PTS Maternal smoking during pregnancy SNP Single nucleotide polymorphismBackgroundThe ﬁeld of epigenetics grew from attempts,beginning over 70years ago,to understand mechanisms whereby multiple cellular phenotypes arise from a single genotype during the complex process of developmental morpho-genesis termed epigenesis.The term ‘‘epigenetics’’was initially reserved for mechanisms by which phenotypic state,as determined by differential gene expression,could be stably retained through cell division by non-genetic factors.Various mechanisms have been proposed to have the potential to encode this phenotypic information;these include enzymatic methylation of cytosine bases (DNAV.K.Cortessis and D.C.Thomas contributed equally to this work.V.K.Cortessis ÁA.J.Levine ÁT.M.Mack ÁR.W.HaileDepartment of Preventive Medicine,Keck School of Medicine,University of Southern California,USC Norris Comprehensive Cancer Center,1441Eastlake Avenue,Los Angeles,CA 90089,USA D.C.Thomas (&)Department of Preventive Medicine,Keck School of Medicine,University of Southern California,2001N.Soto St.,SSB-202F,Los Angeles,CA 90089-9234,USA e-mail:dthomas@C.V.Breton ÁK.D.SiegmundDepartment of Preventive Medicine,Keck School of Medicine,University of Southern California,2001N.Soto St.,Los Angeles,CA 90089-9234,USAirdDepartments of Surgery,Biochemistry and Molecular Biology,Keck School of Medicine,University of Southern California,USC Norris Comprehensive Cancer Center,Epigenome Center,1441Eastlake Avenue,Los Angeles,CA 90089-9601,USAHum Genet (2012)131:1565–1589DOI 10.1007/s00439-012-1189-8methylation),post-translational modiﬁcation of tail domains of histone proteins(histone modiﬁcations)and associated nucleosome positioning or chromatin remodel-ing,non-coding RNAs,and transcription factor regulatory networks(Ptashne2007).Epigenetic marks established by each of these processes are often shared within a cell lineage; however,whether all persisting epigenetic marks satisfy requirements for stable transmission through cell division or some are merely reestablished from other information fol-lowing mitosis remains a vigorously debated question.The term epigenetics has more recently been used in the scientiﬁc literature to describe various unspeciﬁed non-genetic mechanisms inﬂuencing phenotype.This broader usage emerged from mouse studies addressing transgen-erational nutritional effects on phenotype,as well as human studies of phenotypic differences between monozygotic twins.In the popular press‘‘epigenetics’’has become almost synonymous with nutritional and environmental inﬂuences on gene expression.Thus,while‘‘epigenetics’’initially referred to largely self-contained developmental processes,it has come to describe environmental inﬂuences on phenotypic readout of genotypes.This semantic evo-lution has caused confusion and controversy regarding the meaning of‘‘epigenetics’’at a time of intensiﬁed interest in the possible role of epigenetic mechanisms in disease.In this review we deﬁne as epigenetic processes those that stably affect gene expression through mechanisms not involving the primary nucleotide sequence,and epigenetic state as the conﬁguration of chromatin and DNA marks utilized by these processes.By contrast,genetic state is widely understood to refer to the primary nucleotide sequence itself,while genetic processes maintain or change nucleotide sequence.Epidemiologic research addressing epigenetic mecha-nisms as mediators of environmental exposures on disease risk is constrained by important ethical considerations. These often preclude both experimental exposure to candi-date environmental causes,and invasive collection of cell types of greatest developmental and functional relevance to disease processes.Inquiry has therefore progressed largely by integrating information about biological mechanisms obtained in model systems with observational data provided by humans.To address the current state and future promise of this research,we undertook this review with two goals:to illustrate the potential of epigenetic processes to mediate exposure–phenotype relationships and to discuss study design and statistical analysis methods needed to investigate such mechanisms in relation to origins of human disease.We begin by discussing genetic,developmental,and environ-mental determinants of epigenetic state in human and model systems,then describe some of the diverse data implicating epigenetic mechanisms in various human diseases,both within individuals and across generations.We conclude by discussing technical challenges,suggesting promising opportunities for epidemiologic research in environmental epigenetics,and offering some thoughts about translational signiﬁcance and future directions of thisﬁeld. Determinants of epigenetic stateEpigenetic mechanisms work in concert to inﬂuence the potential for gene expression at myriad locations through-out the genome.The resulting epigenetic state of the gen-ome,termed epigenome,varies by cell type.Considering the tremendous diversity of epigenetic marks,which include dozens of different post-translational histone modiﬁcations and more than50million sites of potential DNA methylation in a diploid human genome(and thus [250M possible epigenotypes!),it seems that no two human cells would have identical epigenomes.Indeed,within each individual there are many epigenomes,and these change over time as a consequence of both normal developmental and pathological processes,as well as environmental exposures and random drift.Despite this potential for considerable variability of epigenetic patterns within and between individuals,there can also be remarkable consis-tency.In a study of11tissues in6autopsies,DNA meth-ylation patterns in a highly selected set of loci were found to be highly conserved,with intraclass correlations of0.85 across tissues within individuals and0.83across individ-uals within tissues(Byun et al.2009).The authors inter-preted these patterns as revealing different sets of person-speciﬁc and tissue-speciﬁc differentially methylated genes, anticipating subsequently observed differential genetic and acquired determination(Waterland et al.2010).DNA methylation has been the epigenetic mark most extensively measured in epidemiologic research for numerous reasons.It is of fundamental biological interest owing to its unambiguously stable transmission during cell division.It also has practical advantages:as a chemically stable covalent change to the DNA itself,DNA methylation is the only epi-genetic mark that survives the DNA extraction and puriﬁca-tion that is routine in molecular sample processing,and it can endure decades of archival sample storage(Kristensen et al. 2009).Genetic inﬂuencesNucleotide sequence is a primary determinant of epigenetic state,clearly evident from the distribution of epigenetic marks across the genome,determined in part by direct effects of G:C content and CpG(cytosine-phosphate-guanine dinucleotide) density(Tanay et al.2007;Thomson et al.2010).Additional genetic inﬂuences include proximity to repetitive elements such as Alu and LINE1(Estecio et al.2010),nucleararchitecture(Berman et al.2011),and binding sequences for transacting proteins(Bell et al.2011b;Weth and Renkawitz 2011).Motif searches and screening strategies have identiﬁed sequence elements that predispose to particular epigenetic states(Feltus et al.2006;Ideraabdullah et al.2011;Keshet et al.2006;Lienert et al.2011).Several lines of evidence indicate that genetic poly-morphisms can affect epigenetic state.Greater differences were observed between dizygotic co-twins than between monozygotic co-twins in two forms of epigenetic state: skewed patterns of X-inactivation,and DNA methylation at differentially methylated regions of the imprinted IGF2/ AH19locus(Wong et al.2011;Heijmans et al.2007; Ollikainen et al.2010).Extensive DNA methylation anal-yses in a multigenerational family revealed that epiallelic similarity was greater amongﬁrst-degree relatives than among more distantly related family members.In the same study,analyses addressing both genetic variation and DNA methylation identiﬁed widespread occurrence of allele-speciﬁc DNA methylation(ASM)that was associated with polymorphic nucleotides located near the DNA methyla-tion site,but not parent of origin.Authors of this report concluded that the majority of such ASM events depend on cis-acting DNA sequence(Gertz et al.2011).Such ASM events have yet to be characterized in large population-based studies,but more modest studies addressing hetero-zygous non-imprinted loci have identiﬁed widespread ASMs associated with nearby genotypic polymorphisms in DNA from multiple tissue types(Kerkel et al.2008;Tycko 2010;Schalkwyk et al.2010),as well as allele-speciﬁc chromatin structure and transcription factor binding in lymphoblastoid cell DNA(McDaniell et al.2010,reviewed in Birney et al.2010).Presumed transgenerational inheri-tance of epigenetic changes(‘‘epimutations’’)in the MLH1 (Suter et al.2004)and MSH2(Chan et al.2006)mismatch repair genes,both associated with colorectal cancer,were also traced to germline genetic variation.In the case of the MSH2 epimutation,deletion of a gene immediately upstream of the MSH2gene causes transcription to run through the MSH2 promoter,causing somatic hypermethylation and gene silencing(Ligtenberg et al.2009).The MLH1epimutation was found to be caused by a polymorphism in the50UTR of the MLH1gene,reducing transcriptional activity,and pre-disposing to aberrant somatic DNA methylation in each generation(Hitchins et al.2011).Developmental programming of the epigenomeIn successful mammalian reproduction,the single-cell zygote gives rise to an organism with hundreds of cell types.These diverse cellular phenotypes arise from the same shared genomic sequence by control of the subset of genes expressed in each cell type.Cellular differentiation is tightly linked to extensive erasure and establishment of lineage-speciﬁc epi-genetic marks,a process termed epigenetic reprogramming. Relatively detailed descriptions of DNA methylation in developing tissues have been carried out in the mouse,which serves as a model of epigenetic reprogramming in mammalian development(Trasler2009).At fertilization,reprogramming begins with extensive erasure of methyl marks in DNA of the paternal(sperm-derived)DNA,followed by more general loss of methyl marks in the zygote and embryo during cleavage divisions,while sparing parent-of-origin speciﬁc imprints.By the blastocyst stage,de novo DNA methylation distinguishes inner cell mass cells(from which embryonic lineages arise to create fetal structures)from relatively hypomethylated trophectoderm cells(from which extra-embryonic lineages arise to create transient structures,including placenta)(Fig.1).Germ cell lineage speciﬁcation begins in cells of the proximal epiblast,and involves a second extensive erasure of DNA methylation that removes parental imprint marks (Fig.1).Thereafter,the germ line develops in a sexually dimorphic fashion.New DNA methyl marks are established over many stages,extending through sexual maturity in accordance with the sex of the developing individual.At this time,the sex-speciﬁc imprint marks that govern parent-of-origin speciﬁc expression of imprinted genes in the sub-sequent generation are established(Faulk and Dolinoy2011).Developmental reprogramming can result in dramatic epigenetic differences between the two alleles.The asso-ciation between mono-allelic gene expression and DNA methylation has long been recognized,both in the context of X-inactivation in females(Boggs et al.2002;Sharp et al. 2011)and in parent-of-origin determined genomic imprinting(Ferguson-Smith2011),but now also in the mono-allelic expression of non-imprinted autosomal loci (Harris et al.2010;Tarutani and Takayama2011).Further resetting of epigenetic marks accompanies differ-entiation of many specialized cell types of the body as well as placenta and other transient structures during pregnancy,and subsequent development of body structures during various postnatal stages of development.Chromatin states that arise during development can affect the propensity to subsequent epigenetic change.An example of this is the predisposition of polycomb-repressive complex occupied genes in stem cells to the acquisition of DNA methylation abnormalities in aging and cancer(Ohm et al.2007;Schlesinger et al.2007; Teschendorff et al.2010;Widschwendter et al.2007).Environmental inﬂuencesMultiple differences in gene expression,presumably reﬂecting intrauterine epigenetic differences,have been identiﬁed in several tissues from newborn identical twins (Gordon et al.2011).The global methylation pattern ofindividuals changes with increasing age (Bjornsson et al.2008),as does the difference in global methylation between MZ twin pairs (Fraga et al.2005).Genetically identical MZ twins show some epigenetic discordance at birth,as indi-cated by gene expression discordance (Gordon et al.2011).Even over the ﬁrst decade of life (Wong et al.2010),and as aging adults (Talens et al.2010),MZ twins acquire addi-tional differences in epigenetic state,which may partly reﬂect different exposure histories,as would be expected if environmental exposures inﬂuence epigenetic state.How-ever,stochastic drift in epigenetic state and related con-sequences such as mono-allelic expression described in the previous section is likely responsible for much of the observed divergence.Therefore,other forms of data (dis-cussed below)are needed to determine what type of exposures may inﬂuence epigenetic state and the extent of resulting changes.Experimental studiesThe most direct evidence suggesting that ambient exposures may inﬂuence epigenetic state is experimental.In vitro studies have demonstrated associations of DNA methylation with various metals (Dolinoy et al.2007b ;Wright and Baccarelli 2007).In the in vivo setting,prenatal protein restriction is associated with hypomethylation of the gluco-corticoid receptor (GR )and PPAR a gene promoter regions inrat liver (Lillycrop et al.2005),changes that were prevented by folic acid supplementation (Lillycrop et al.2005)and which were transmitted to the F2generation (Burdge et al.2007).Plagemann et al.(2009)found hypermethylation in the promoter of the anorexigenic gene for proopiomelano-cortin in rats overfed as neonates.Whether this change could be transmitted to offspring was not assessed.DNA from sperm of mice exposed to steel plant air was found to be persistently hypermethylated long after exposure ended (Yauk et al.2008).Additionally,maternal nurturing behav-ior has been shown to modify methylation at individual CpG sites in the ngf1a binding region of the GR gene in the hip-pocampus of the offspring (Weaver et al.2004),an epige-netic modiﬁcation that persisted both into adulthood to modify response to stress,and into the F2generation.Human studiesChristensen and Marsit (2011)and Terry et al.(2011)have provided comprehensive reviews of environmental inﬂu-ences on epigenetic state in humans.Here we note expo-sure periods of particular interest and several examples of environmental exposures reportedly associated with epi-genetic state of speciﬁc human cell types.The epigenome may be most vulnerable to environ-mental insults during periods of extensive epigenetic reprogramming,which may in theory be disruptedbyFig.1Reprogramming ofDNA methylation in the zygote,early embryo,and primordial germ cells.Thickness of the outer arrows indicates levels of DNA methylation.Red maternal genome,blue paternal genome,black diploid genome.Embryonic lineages arise from cells of the inner cell mass (ICM),the placenta and extraembryonic membranes from trophectoderm cells,and the germ cell lineage fromprimordial germ cells following their determination fromproximal epiblast.Inner circles indicate developmental stages when key elements ofepigenetic programming are thought to occur (Adapted from Feng et al.2010)exposures that interfere with any process that governs reprogramming.Periods of particular vulnerability may therefore include the early stages of embryonic develop-ment mentioned above.Childhood is also proposed as a period of vulnerability,especially in the germline of females,since oocytes remain in a haploid de-methylated state until puberty,so environmental insults may poten-tially disturb the epigenetic state of the oocyte for many years(Faulk and Dolinoy2011),with potential implica-tions for both fertility and initial epigenetic state of off-spring of an exposed female.Somatic changes to DNA methylation may also result from environmental exposures in adults,as have been observed in aging and disease processes such as cancer described in the next section. Energy and nutrient intakeSigniﬁcant epigenetic changes in the IGF2gene have been documented in those prenatally exposed to severe caloric restriction during the Dutch hunger winter of World War II (Heijmans et al.2008).Hughes et al.(2009)additionally found that those most likely to be exposed to this famine during adolescence or young adulthood had a signiﬁcantly decreased risk of developing colorectal cancers(CRC) characterized by the CpG island methylator phenotype (CIMP),suggesting a role for early life exposures in CIMP-speciﬁc CRC pathogenesis.Folates are the major source of the methyl groups used for DNA and histone methylation.One study of folates and other one-carbon nutrients reported a differential effect of folate on the risk of the CIMP CRC subset compared to the non-CIMP subset(Van Guelpen et al.2010),while two other studies did not(Slattery et al.2006;van den Donk et al.2007).Most studies of the microsatellite instability high subset,characterized by hypermethylation of the MLH1gene promoter region and CIMP(Weisenberger et al.2006),have yielded similarly negative results(Eaton et al.2005;Schernhammer et al.2008;Slattery et al.2001; Wark et al.2005).On the other hand,in some studies the association between intake of alcohol(which degrades folates)and CRC risk has been reported to be greater in MSI-H and CIMP tumors(Diergaarde et al.2003;Eaton et al.2005;Slattery et al.2001).Micro-RNAs(miRNAs)are very short non-coding RNA molecules that can downregulate protein-coding genes by destabilizing mRNAs or blocking translation.The possi-bility that exogenous microRNA consumed in food may epigenetically regulate gene expression has emerged from recent studies demonstrating the presence of plant-derived miRNAs in sera of humans and other mammals(Zhang et al.2012).One of these plant microRNAs,MIR168a, which was demonstrated to be only of plant origin in control mice,binds coding sequence of the mammalian LDLRAP1 gene in vitro.Functional consequences in mammalian sys-tems were demonstrated experimentally,as MIR168a administered in vitro and during in vivo feeding studies decreased expression of the protein product of LDLRAP1. This line of research suggests novel epigenetic mechanisms whereby diet may modify risk of human disease.Air pollutionEmerging evidence suggests that air pollutants can inﬂu-ence epigenetic changes,including DNA methylation as well as up-or down-regulation of miRNAs(Jardim2011). In human epidemiologic studies,PM2.5and PM10expo-sures are associated with hypomethylation of Alu and/or LINE1elements in leukocytes and buccal cells(Baccarelli et al.2009;Bollati and Baccarelli2010;Madrigano et al. 2011;Salam et al.2012;Tarantini et al.2009),as well as altered DNA methylation in NOS2A,a gene involved in production of nitric oxide(Salam et al.2012;Tarantini et al.2009).Living in highly polluted cities(high PM and ozone)is also associated with hypermethylation of FOXP3 in regulatory T cells(Nadeau et al.2010),while neonates who were prenatally exposed to polyaromatic hydrocarbon (PAH)had hypermethylated ACSL3in DNA of umbilical cord white blood cells(Perera et al.2009);notably,both of these genes are involved in asthma pathogenesis.PAHs are also associated with hypermethylation of LINE1and Alu (Pavanello et al.2009;Perera et al.2009).More limited evidence is emerging to suggest that air pollution is asso-ciated with changes in miRNA expression(Bollati et al. 2010;Jardim2011),and adverse effects of air pollution constituents may be modiﬁed by variant alleles of genes involved in miRNA processing(Wilker et al.2010). Tobacco smokeFetal exposure to maternal smoking during pregnancy (PTS)is associated with reduced methylation of several repeated sequences,including Sat2(Flom et al.2011),Alu, and LINE1among children with the GSTM1null genotype (Breton et al.2009).PTS exposure is also associated with increased DNA methylation in speciﬁc genes,such as AXL and PTPRO(Breton et al.2009,2011b)and IGF2(Murphy et al.2011).In adult lung cancer patients,quantity and duration of active smoking as well as second-hand smoke is associated with increased DNA methylation of p16(Kim et al.2001;Scesnaite et al.2012),MGMT,and DAPK (Russo et al.2005).Tobacco smoke is also associated with tumor cell DNA methylation changes in esophageal squa-mous cell carcinoma(Huang et al.2011),signiﬁcantly higher frequencies of abnormal DNA hypermethylation inprostate(Enokida et al.2006)and gastric cancers tumor cells(Nan et al.2005)and with a higher risk of CIMP?colorectal tumors(Limsui et al.2010;Samowitz et al.2006).Lastly,the F2RL3gene is hypomethylated in smokers and may mediate the detrimental impact of smoking on cardiovascular mortality,since hypomethylat-ed F2RL3was found to be strongly associated with car-diovascular mortality among patients with stable coronary heart disease(Breitling et al.2012).Oxidative stressReactive oxygen species(ROS)are involved in numerous cellular processes including cellular redox alterations, immune response,signaling pathways,chromatin remod-eling and gene expression(Sundar et al.2010).ROS have the potential to inﬂuence epigenetic mechanisms(Baccar-elli and Bollati2009),and have been shown to inhibit binding of methyl-CpG binding protein2,a critical epi-genetic regulator that recruits cytosine methyl transferases and histone deacetylases to DNA(Valinluck et al.2004). Numerous environmental exposures,including constituents of air pollution and tobacco smoke,can generate ROS and thus may potentially alter epigenetic processes through oxidative stress mechanisms.MetalsPrenatal lead exposure is associated with decreased meth-ylation of LINE1and Alu in cord blood(Pilsner et al. 2009),and a similar pattern of LINE1methylation was reported in an elderly cohort(Wright et al.2010).Studies in humans have shown that arsenic exposure is associated with either global hypermethylation or hypomethylation in peripheral blood mononuclear cells(PBMCs)depending on dose(Majumdar et al.2010),as well as DNA hyperme-thylation of several genes,including CDKN2A(Chanda et al.2006),RASSF1A and PRSS3(Marsit et al.2006). Exposure to airborne particulates rich in lead,cadmium and chromium are associated with miRNA expression in peripheral blood(Bollati et al.2010)and airborne levels of nickel and arsenic are positively correlated with both his-tone3-lysine4trimethylation(H3K4me3)and histone 3-lysine9acetylation(H3K9ac)in blood leukocytes (Cantone et al.2011).Occupational exposure to nickel is associated with increased H3K4me3and decreased H3K9me2in PBMCs(Arita et al.2011).Lastly,cadmium can induce overexpression of the DNA methyltransferase genes DNMT1and DNMT3a in human embryo lung ﬁbroblasts,and is associated with hypermethylation and silencing of the MSH2,ERCC1,XRCC1and OGG1genes in human bronchial epithelial cells(Jiang et al.2008;Zhou et al.2011).Organic chemicalsGas-station attendants and police ofﬁcers occupationally exposed to low levels of benzene were found to have signiﬁcantly lower LINE1and Alu methylation,hyper-methylation of p15,and hypomethylation of MAGE-1in blood(Bollati and Baccarelli2010;Bollati et al.2007).Genetic9epigenetic9environmental interactionsMost work investigating effects of environmental factors on epigenetic state has not considered the potential for genetic susceptibility to modify these associations.However,Salam et al.(2012)recently investigated contributions of both genetic and epigenetic variation in air pollution-mediated levels of fractional exhaled nitric oxide(feNO).Measure-ment of feNO provides an in vivo summary assessment of inducible nitric oxide synthase(iNOS)activity as well as airway inﬂammation.These investigators found interrelated effects of exposure to the air pollution constituents PM2.5, NOS2A promoter haplotypes,and methylation of the iNOS encoding gene NOS2A and NOS2promotor haplotypes on feNO level.These observations illustrate not only the feasi-bility of assessing interactions between epigenetic,genetic, and environmental factors,but also the importance of doing so in order to delineate complex biological relationships and identify susceptible subpopulations.Epigenetic effects in human diseaseConditions associated with improper parental contributions of imprinted genes are currently the clearest examples of human diseases related to epigenetic state.Even before genomic imprinting was described,experiments in which pronuclei were transplanted into enucleated eggs demon-strated that both maternal and paternal chromosomal con-tributions are required for normal development.Control conceptuses receiving one set(haploid genome)of mater-nal(egg-derived)and one set of paternal(sperm-derived) chromosomes could develop normally.However,abnormal development and early demise occurred in all conceptuses receiving either two maternal sets or two paternal sets of chromosomes(McGrath and Solter1984),which devel-oped into tissues with histologic features of dermoid cysts and hydatiform moles,respectively.Model imprinting disorders such as Beckwith–Wiede-mann,Angelman,Russell–Silver,and Prader–Willi syn-dromes are human conditions that can be caused by aberrant epigenetic state(Ferguson-Smith2011).The speciﬁc features,early onset,and rarity of these disorders facilitated recognition of their relation to improper parental contributions of imprinted loci(e.g.two maternal or two。

(完整版)Epigenetics glossary表观遗传名词解释

(5-fc）
5—methylcytosine during its active
demethylation by the TET enzymes 。 It is
Байду номын сангаас
enriched at poised enhancers and other
regulatory regions。
5-hydroxymethylcy The first oxidized derivative of
Epigenetics glossary
(完整版)Epigenetics glossary 表观遗传名词解释
Discover our epigenetics glossary with definitions covering the need—to—know terms
inepigenetics.
Key term
Definition
3C (Chromosome A technique used to quantify specific chromatin
Conformation
interactions
of
interest in
Capture)
vivo 。 Cross-linked restriction digested
Bisulfite sequencing
Amplification of bisulfite converted DNA with PCR followed by DNA sequencing to differentiate unmodified cytosine from 5-methylcytosine。 It can be applied to specific regions or the entire genome。

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- RIZ1
RIZ2 -
- Lsd1
只有底物亲和力低(Km高)的甲基化酶才能被一号饮食上调
底物亲和力 Km (M) GNMT TEMT/INMT GAMT PRMT1 COMT TPMT PCMT ICMT DNMT1 100 54 49 8 3.1 3 2 2.1 1.4 表达倍数差饮食一号／二号 4.2 9.7 2.2 0.9 0.9 1.0 1.0 0.9 1.1
Epigenetic Inheritance
• Transmission of non-DNA sequence information through either meiosis or mitosis • When a methylated DNA sequence replicates, only one strand of the next-generation double helix has all its methyl markers intact; the other strand needs to be remethylated • Maintenance methylase theory
• Pathogenesis of diseases
Molecular Mechanisms that Mediate Epigenetic Phenomena
• DNA methylation (CpG dinucleotides) • Histone modifications
Nucleosome
PRDM2/RIZ1 是第一个甲基化酶抑癌基因
• • • •
在大量肿瘤中表达关闭在部分癌症中发生突变抑制细胞生长在小鼠内剔除可造成癌症
营养失调致癌机理新假说
过量动物蛋白摄取大部分细胞长期处在SAM/SAH低比例状态 RIZ1蛋白在大部分细胞内长期处在被抑制状态癌症
如何寻找在甲基营养预防癌症中起限速作用的基因？
癌症流行病学现状第一个甲基化酶抑癌基因RIZ1
第一个饮食防Байду номын сангаас的限速步骤，RIZ1通路
美国癌症现状
• 第二大死因 (每年死亡人数的~24%) • 每年110 万新病人（癌症发生率是中国的2.4倍）
• 30－70％的肿瘤可通过食物来预防
西方式食物中的哪些因素与癌症有关？
重要因素：营养成分失衡过量红肉
RIZ1存在与否对一号饮食的防癌功效起关键作用但不影响二号饮食的致癌功效
一号饮食小鼠存活曲线图
二号饮食小鼠存活曲线图
野生型
野生型剔除型剔除型
只有极少数甲基化酶可被饮食调控
表达倍数差：饮食一号／二号
一号防癌型饮食可提高RIZ1蛋白的表达水平
Diet 1
-/+/+
Diet 2
+/+ RIZ1 genotype
– DNA methyltransferases (DNMTs): Enzymes that transfer methyl groups to cytosine nucleotides – DNMTs transfer methyl groups to the naked cytosines based on the methylation template provided by the other strand-
动物模型: RIZ1剔除小鼠（RIZ1-/-）并含有p53+/- 杂合突变
一号防癌型饮食需要RIZ1才能起作用
相对于二号致癌型饮食，一号防癌型饮食可对野生型小鼠起到更多的防癌功效，但对于RIZ1剔除的小鼠却不能
野生型小鼠存活曲线图
RIZ1剔除型小鼠存活曲线图
一号
一号
二号
二号
RIZ1需要一号健康饮食才能起作用
酶活力与底物亲和力及浓度的关系米－曼方程曲线图
酶反应速度
Km
底物浓度
RIZ1下游靶基因
RIZ1 repressed genes (54) 生长调控: Jun, Fos, Egr1, Gdf15, Ctgf, Pfkfb3, NRK1, G0S2, Nrg4, Sirt1 信号转递: Ppp1r3g, Hrasls3 代谢: Mthfd1l, Abcc4, Alas1, Ccrn4l, Lpin1, Upp2, Thrsp, Pte2a, Ren1, Necap2, Cyp7a1 Cyp4a14, Per1 运输: Kcnk5, Mfsd2 未知: LOC329554, LOC333621, 1810011O10Rik, LOC380906, 1700018O18Rik, 6430406H24Rik, 2310011C19Rik, Igsf10, LOC241901, Igl-V1, Ibrdc3, 1110028A07Rik, LOC229599, LOC241901, Tsku, Coq10b/1500041J02Rik, 4833416J08Rik, 9530025L08Rik, 8430403J19Rik, Bhlhb9, Endod1, Tmc7, Cd79b, LOC194586 RIZ1 activated genes (43) 生长调控: Nrp1,Tgfb1i4, Gadd45g, Sox9, Dmbt1, Idb2, Nxf1, Cited2, Fmn2, Bcl6 信号转递: Socs3, Socs2, Insig2, Rasl11b 代谢: Acaca, Ugt1a6, Elovl3, Chk, Hnrpk, Serpina9 运输: Gjb2, Slc25a30 未知: AK041123.1, 1110067D22Rik, Hrg, B930007L02Rik, 2810411C16Rik, Rnf125, 4930588K23Rik, B230314M03Rik, 2810405K07Rik, Rutbc2, D830014E11Rik, 9530029F08Rik, 2900064B18Rik, 2700060E02Rik, BC003277, 5033430I15Rik, LOC383483, LOC381534, 2310035P21Rik, LOC383125, LOC239727
Epigenetic Regulation of Gene Expression
Methylated DNA
Histone
Histone Modification Status Correlates with Transcriptional Activity
• Gene activation correlated with H3-K9 acetylation • Gene silencing associated with H3-K9 methylation
缺乏蔬菜及水果非重要因素：突变剂
食物添加剂，污染物，等等
白肉比红肉好吗?
红肉
白肉
甲基营养成分的代谢途径
蛋氨酸 S-腺苷甲硫氨酸甲基化酶
S-腺苷高半胱氨酸
Huang, 2002, Nature Rev Cancer, 2:469-476
甲基营养成分比例失衡可导致低比例 SAM/SAH 及癌症
在所有可能的营养成分比例失衡的状况中，甲基
营养成分比例失衡是唯一能单独造成癌症的。
- 蛋氨酸摄取过高或过低都可在小鼠体内造成癌症。
癌症防治与机理研究中的最大挑战
环境因子
癌症
甲基转移酶
DNA RNA 脂肪及相关代谢物蛋白质/组蛋白
S-Adenosyl Methionine (SAM) S-腺苷甲硫氨酸
Antibody Chromatin and/or Transcriptional Factors
Cy5 Labeled Targets Cy3 Labeled Targets
Agilent 185K oligonucleotide tiling array
Epigenetics and Cancer
Chromatin Immunoprecipitation Microarray
Crosslink and sonicate Antibody binding
Immunoprecipitate
IP
Input
Label with fluorescent dyes
Co-hybridize onto oligonucleotide array
• Gene-regulatory information that is not expressed in DNA sequences is transmitted from one generation (of cells or organisms) to the next
Epigenetics and Different Aspects of Life
• Development of multicellular organism • Environment-organism interaction
For examples: Nutrition supplements and environmental toxins
Image: Randy Jirtle
Histone Modifications
Adapted from Lund and Lohuizen Genes Dev 2004
Epigenetic Regulation of Gene Expression
• Epigenetic information modulates gene expression without modifying actual DNA sequence • Histone modifications change the chromatin structure and affect the accessibility of DNA to regulatory proteins