Tissue-specific direct targets of Caenorhabditis elegans RbE2F dictate distinct somatic and germline programs 英文参考文献.docVIP

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Tissue-specific direct targets of Caenorhabditis elegans RbE2F dictate distinct somatic and germline programs 英文参考文献.doc

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Tissue-specific direct targets of Caenorhabditis elegans RbE2F dictate distinct somatic and germline programs 英文参考文献

Kudronetal.GenomeBiology2013,14:R5 /2013/14/1/R5 RESEARCH OpenAccess Tissue-specificdirecttargetsofCaenorhabditis elegansRb/E2Fdictatedistinctsomaticand germlineprograms MichelleKudron1,WeiNiu1,ZhiLu2,3,GuilinWang1,MarkGerstein3,MichaelSnyder4andValerieReinke1* Abstract Background:ThetumorsuppressorRb/E2Fregulatesgeneexpressiontocontroldifferentiationinmultipletissues duringdevelopment,althoughhowitdirectstissue-specificgeneregulationinvivoispoorlyunderstood. Results:Wedeterminedthegenome-widebindingprofilesforCaenorhabditiselegansRb/E2F-likecomponentsin thegermline,intheintestineandbroadlythroughoutthesoma,anduncoveredhighlytissue-specificbinding patternsandtargetgenes.ChromatinassociationbyLIN-35,theC.elegansorthologofRb,isimpairedinthe germlinebutrobustinthesoma,acharacteristicthatmightgoverndifferentialeffectsongeneexpressioninthe twocelltypes.Intheintestine,LIN-35andtheheterochromatinproteinHPL-2,theorthologofHp1,coordinately bindatmanysiteslackingE2F.Finally,selecteddirecttargetgenescontributetothesoma-to-germline transformationoflin-35mutants,includingmes-4,asoma-specifictargetthatpromotesH3K36methylation,and csr-1,agermline-specifictargetthatfunctionsina22GsmallRNApathway. Conclusions:Insum,identificationoftissue-specificbindingprofilesandeffectortargetgenesrevealsimportant insightsintothemechanismsbywhichRb/E2Fcontrolsdistinctcellfatesinvivo. Background analysesofmammalianRb/E2Fhavebeenperformedin TheRb/E2Ftranscriptionalcomplexisamajorregulator tissueculture,oftenintransformedcelllines(forexam- of developmental and cellular fates. Underscoring its ple, [3,4]). While valuable, the resulting global DNA importance, the pocket protein Rbacts as a key tumor binding profiles of Rb and E2F can be correlated only suppressor protein in cancers of diverse tissue origin indirectlywithtissue-specificphenotypesandultimately (reviewedin[1]).Rbactsinlargepartbyregulatingthe withtumorigenesis. activity ofE2F,aheterodimeric sequence-specific DNA The nemato