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HEREDITAS(Beijing)20114,33(4):285―292ISSN0253-9772综述收稿日期:2010−09−25;修回日期:2010−12−20基金项目:(90919030,30921062)作者简介:,,E-mail:songboyan@bjmu.edu.cn通讯作者:,,,E-mail:zhuweiguo@bjmu.edu.cnDOI:10.3724/SP.J.1005.2011.00285组蛋白甲基化修饰效应分子的研究进展宋博研,朱卫国,100191作为一种重要的表观遗传学调控机制,组蛋白甲基化修饰在多种生命过程中发挥了重要的作用。细胞内有多种组蛋白甲基化酶和去甲基化酶共同调节组蛋白的修饰状态,在组蛋白甲基化状态确定后,多种效应分子特异的读取修饰信息,从而参与基因转录调控过程。文章从组蛋白甲基化效应分子的作用机制方面综述了这一领域的研究进展。表观遗传学;组蛋白修饰;组蛋白甲基化修饰效应蛋白;基因转录调控AdvancesineffectorproteinofhistonemethylationSONGBo-Yan,ZHUWei-GuoDepartmentofBiochemistryandMolecularBiology,HealthScienceCenter,PekingUniversity,Beijing100191,ChinaAbstract:Asasignificantepigeneticregulationmechanism,histonemethylationplaysanimportantroleinmanybiologi-calprocesses.Incells,therearevarioushistonemethyltransferasesandhistonedemethylasesworkingcooperativelytore-gulatethehistonemethylationstate.Uponhistonemodification,effectorproteinsrecognizemodificationsitesspecifically,andaffectgenetranscriptionalprocess.Thisreviewmainlyfocusesonrecentadvancesinhistonemethylationeffectorpro-tein’sfunctionmechanism.Keywords:epigenetics;histonemodification;effectorproteinofmethylatedhistone;genetranscriptionregulation,H2AH2BH3H4,146bpDNAH3H4NSUMODNA,DNADNA,“”,“”“”(Writer)“”(Eraser)(Effector),“”,(Histonemethyltransferase)“”,(Histonedemethylase)“”“”,“”,“”,,--DNA286HEREDITAS(Beijing)2011331,ChromodomainTudordomainMBTdomainPHDdomainWDR40repeatsAnkyrinrepeats4:(1);(2)ATP;(3);(4),[1],(K)(R)H349273679(H3K4H3K9H3K27H3K36H3K79),H420(H4K20)H3K4H3K36H3K79,H3K9H3K27H4K20H3281726(H3R2H3R8H3R17H3R26),H43(H4R3),(me1)(me2)(me3)(,3)RNAⅡH3K4DNA,(Histoneacetyltansferase,HAT),,,,,,[2]DNADNA(DNAmethyltransferase,Dnmt)DNACpG5,DNADNA,,[3]DNADNA(Methyl-CpG-bindingproteins,MBP)(Histonedeacetylase,HDAC),,[4]DNA,,H3K4me3H3K36me3DNAH3K9me3H3K27me3H4K20me3DNA[5],H3K4me3HAT,,,DNA,,H3K4me3/,H3K4me3,H3K9me3,,H3K9me3H3K27me3H4K20me3HDAC,表1效应分子及其结构域ChromodomainH3K4me1/2/3,H3K9me2/3,HP1,Polycomb,CHD1,MRG15H3k27me3,H3K36me2/3TudorH3K4me3,H4K20me1/2/3MJD2A,53BP1MBTH1Bk26me1/2,H4K20me1/2L3MBTL1PHDH3K4me0/2/3,H3K9me3BHC80,ING2,BPTF,JARID1CWDR40H3K4me2,H3R2WDR5AnkyrinrepeatsH3K9me1/2G9a,GLP4:287,,H3K9me3H4K20me3,,,,11.1H3K4H3K4,,[5]H3K4MLL(Mixedlineageleukemia),MLL1MLL2MLL3MLL4SET1ASET1BASH1,H3K4TAF3INGCHD1BPTFWDR5JMJD2ABHC801,H3K4,图1组蛋白H3K4效应分子作用方式H3K4,TAF3TFⅡD,TAF3PHDdomainH3K4me3,TFⅡDH3K4me3,,,H3K9K3K14TFⅡDH3K4me3BPTFING2H3K4me3,TAF3H3K4me3BPTFING210~20[6]H3K4me3,H3K4,NURFBPTFPHDdomainH3K4me2/3[7],SNF2LATP,ATP,HOXC8[8],,CHD1H3K4me3U2snRNPFACT/PAF,mRNA[9]ING(Inhibitorofgrowth)PHDdomainH3K4me2/3,,ING,DNA,p53,[10]ING4HBO1(HistoneacetyltransferasebindingtoORC),ING4H3K4me3HBO1,,DNA,ING4,,[11],H3K4,,ING2H3K4ING2mSin3a-HDAC1,DNA,ING2PHDdomainH3K4me3mSin3a-HDAC1,,,DNA[12],ING1DNAH3K4me3[13],ING2ING4,H3K4MLLWDR5ASH2RbBP5MLL288HEREDITAS(Beijing)201133WDR5H3K4me2,,MLL,H3K4me2H3K4me3JMJD2AtudordomainH3K4me3,H3K9me2/3H3K36me2/3,JMJD2A[14]LSD1BHC80PHDdomainH3K4,LSD1H3K4[15]H3K4,1.2H3K9H3K9,H3K9:SUV39H1,SUV39H2,G9a,ESET/SETDB1EuHMTase/GLPH3K9HP1(Heterochromatinbindingprotein1)UHRF1(Ubiquitin-like,containingPHD,RINGfingerdomains1)2,H3K9RNAⅡ图2组蛋白H3K9效应分子作用方式,HP1Chp2Swi6Chp2H3K9SHRE2H3K14,RNAⅡ,,Swi6H3K9,siRNA,[16],HP1,HP13:HP1α,HP1βHP1γHP1αHP1β,HP1γHP1αHP1γDNAKu70,[17]HP1DNMT1DNMT3ADNAH3K9,DNA,,SUV39H1DNA,depsipeptide,H3K9G9aSUV39H1,p16H3K9me2/3,HP1DNMT1,DNA,p16[18]depsipeptideDNA,H3K9DNA,DNAMeCP2H3K9,DNAH3K9[19],DNADNA,,DNA,DNA,DNA,,HP1H3K9HP1,HP1αchromoshadowdomainH3K36me2/3dKDMA4A,RNAⅡ,dKDMA4AHP1α,H3K9,[20],RbSUV39H1HP1,4:289cyclinEH3K9,cyclinE[21],THP-1,G9aTNFα,G9aH3K9,HP1H3K9me2DNMTa/3b,DNA,TNFα[22],HP1HP1H3K9me2/3,SUV39H1,H3K9HP1SUV39H1,H3K9me3[23]HP1H4K20SUV420H2,HP1SUV420H2,H4K20,[24]DNAUVDNA,HP1H3K9me3,HP1UVHP1DNA[25]UHRF1(ICBP90/NP95)1998UHRF1PHDdomainH3K9me2/3,G9aHDAC1p21[26]G1/S,UHRF11.3H3K27H3K27,PolycombResponseElements(PREs),XH3K27EZH2H3K27PolycombPolycombRepressivecomplex(PRC)PRC1PRC2,PolycombPRC1PRC1PolycombH3K27me3,[27],H3K27UTXHoxH3K27me2/me3,PRC1[28]PRC1H3K27me3,PRC1,,PRC1ES,H3K4H3K27,H2A3RNAⅡ,[29]PRC1RING1RING1B,H2A,[30],H2AFACT(FACTRNA)[31]PRC1H2A,PRC1H3K27me3PRC2PRC1,PRC1H2A,PRC2H3K27,RNA,[31],H3K27me31.4H3K36H3K36H3K36:SET2,NSD1,SYMD2Rpd3SEaf3Rco1chromodomainPHDdomainH3K36me[32],RNAⅡC2,Paf1Set2ORF,H3K36,Rpd3S,RNAⅡ,[33,34]1.5H3K79H3K79,H3K79DOT1,DNA290HEREDITAS(Beijing)20113353BP1tandomtudordomainH3K79me253BP1DNA(DNAdoublestrandbreaks,DSBs),p53,DNA[35]1.6H4K20H4K20DNAH4K20:Pr-SET7/8,SUV4-20H1,SUV4-20H2,H4K20Crb2,Pdp1L3MBTL1Crb2DNA,H4K20me2,Crb2tandemtudordomain,DSBs,G2/M[36],Pdp1PWWPdomainH4K20me1,Set9Set9H4K20me1H4K20me3,L3MBTL1MBTdomainH4K20me1,[37],L3MBTL1PR-SET7,H4K20me1H4K20me2[38]2,PRMT1PRMT2PRMT3PRMT4PRMT5PRMT6PRMT7PRMT8PRMT9,PRMT5H4R3,DNADNMT3A,DNA,[39],,peptidepull-down,,,,[40],,3,RNAⅡ,,DNA,,“”,,,,,,,,参考文献(References):[1]RuthenburgAJ,AllisCD,WysockaJ.Methylationofly-sine4onhistoneH3:intricacyofwritingandreadingasingleepigeneticmark.MolCell,2007,25(1):15−30.[2]KouzaridesT.Chromatinmodificationsandtheirfunction.Cell,2007,128(4):693−705.[3]WattF,MolloyPL.CytosinemethylationpreventsbindingtoDNAofaHeLacelltr
本文标题:组蛋白甲基化修饰效应分子的研究进展_宋博研
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