DEVELOPMENTATAGLANCECellfatecontrolbypioneertranscriptionfactorsMakikoIwafuchi-DoiandKennethS.Zaret*ABSTRACTDistinctcombinationsoftranscriptionfactorsarenecessarytoelicitcellfatechangesinembryonicdevelopment.Yetwithineachgroupoffate-changingtranscriptionfactors,asubsetcalled‘pioneerfactors’aredominantintheirabilitytoengagesilent,unmarkedchromatinandinitiatetherecruitmentofotherfactors,therebyimpartingnewfunctiontoregulatoryDNAsequences.Recentstudieshaveshownthatpioneerfactorsarealsocrucialforcellularreprogrammingandthattheyareimplicatedinthemarkedchangesingeneregulatorynetworksthatoccurinvariouscancers.Here,weprovideanoverviewofthecontextsinwhichpioneerfactorsfunction,howtheycantargetsilentgenes,andtheirlimitationsatregionsofheterochromatin.Understandinghowpioneerfactorsregulategeneexpressiongreatlyenhancesourunderstandingofhowspecificdevelopmentallineagesareestablishedaswellashowcellfatescanbemanipulated.KEYWORDS:Cellfatecontrol,Pioneerfactors,TranscriptionIntroductionAdifferentiated,multicellularorganismismadeupofdiversecelltypesthatareinducedandmaintainedbycelltype-specificchromatinstatesandpatternsofgeneexpression.Whennewcellfatesareinducedduringembryonicdevelopment,tissueregenerationorcellreprogramming,regulatorytranscriptionfactorsmustsuppressgenesspecifictotheoriginalcellfateandactivategenesspecifictothenewcellfate.Ratherthanoneregulatoryproteinbeingsingularlyresponsiblefordeterminingeachcelltype,itiswellestablishedthatparticularcombinationsoftranscriptionfactorselicitcellfatechangesandmaintaincellidentity(Yamamoto,1985).Butalthoughgroupsoftranscriptionfactorselicitcellfatechanges,eachmemberofagroupdoesnotfunctionidenticallyinthemechanismofchanginggeneexpressionpatterns.Dataderivedfromchromatin-bindingstudiesinembryos,biochemicalreconstitutionofchromatininvitro,genomics,andgeneticshaverevealedthatcertaintranscriptionfactors,termed‘pioneerfactors’,havethedistinctabilitytotargetnucleosomalDNAsitesatsilentgenesthathavenotbeenmarkedforactivity,andthusiniti...
