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
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
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