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ID:58885570
大小:2.23 MB
页数:32页
时间:2020-09-30
《DNA甲基化功能全解ppt课件.ppt》由会员上传分享,免费在线阅读,更多相关内容在教育资源-天天文库。
1、DNAmethylationDNA甲基化功能1Afewdatahumangenome:about28milionCpGs60–80%aregenerallymethylated.Lessthan10%ofCpGsoccurinCG-denseregionsthataretermedCpGislands;HalfofCGIoccuratgenebody.Afewknowledge1.ThreeconservedenzymesDNAmethyltransferase1(DNMT1):DNAmethylationmaintenan
2、ceDNMT3AandDNMT3B:denovomethylationDNMT3L:isacatalyticallyinactivehomologueofDNMT3AandDNMT3B2.Demethylation:thymidineDNAglycosylase(TDG)teneleventranslocationmethylatosinedioxygenase(TET)activation-inducedcytodinedeaminase(AID)ThemanyrolesofDNAmethylationDNMT1DNMT3
3、A/BMarkingactiveregulatoryelementsTFStadleretal,Nature,2011Imprinting♀♂Brandeisetal,EMBOJ,1993AlternativepromoterregulationMaunakeaetal,Nature,2010SilencingofrepeatsAlu/LINE/SINEWalshetal,NatGenetics,1998GenesilencingNaveh-ManyandCedar,PNAS,1981CytosineMethyl-cytos
4、ineKnownfeaturesofDNAmethylationinmammalsunknownfeaturesofDNAmethylationinmammalsFUNCTIONS转录起始位点的甲基化:有CpG岛的模式,没有CpG岛的模式Genebody的甲基化增强子的甲基化绝缘子的甲基化PatternsatCpGislandtranscriptionstartsites大多数的CGIs保持不甲基化的状态。当在活跃的TSS有CGIs时,他们的启动子区域往往有NDRs(核小体贫乏区域),并且NDRs周围存在核小体变体H2A.Z
5、,和H3K4me3。CGI启动子能够被很多的机制所抑制,比如,myogenicdifferentiation1(MYOD1)orpairedbox6(PAX6)被polycomb蛋白,被抑制的启动子TSS区有核小体以及H3K27me3.许多被抑制的基因同样存在CGIs的甲基化。这些被甲基化的启动子区域的CGIs大多数都是长时期的稳定的抑制状态。(例如,印记基因)Patternsatnon-CpG-islandTSSs1.在TSS区域CpG-poor时,表达的基因往往是未甲基化的,而不表达的基因往往是甲基化的。比如OCT4an
6、dNANOGpromoters。2.但是在05年的全基因组层面上,发现甲基化和表达上没有负相关,但是在08年重分析又发现这个负相关的规律是存在。3.一个问题是究竟甲基化是表达沉默的原因,还是结果。Reasonorresultresult:methylationoftheHprtgeneontheinactiveXchromosomeoccurredafterthechromosomehadbeeninactivatedreason:studyshowedthatthemethylasewasessentialfordiffe
7、rentiationofafairlyshort-livedcelltype,itseemspossiblethatDNAmethylationhasamoreinstructiveroleininitiatingratherthanreinforcingthesilencingGenome-widestudiesincancercellshave,however,shownthatgeneswithCGIpromotersthatarealreadysilencedbyPolycombcomplexesaremuchmor
8、elikelythanothergenestobecomemethylatedincancer:thatis,thesilentstateprecedesmethylation主流的观点是:DNA甲基化只是起到维持沉默的作用Genebodymethylation1.在外显子区域的DNA甲基
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