组蛋白甲基化修饰效应分子的研究进展_宋博研

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:[e-mail]通讯作者:,,,E-mail:[e-mail]: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