The C. elegans CBFβ homolog, BRO-1, regulates the proliferation, differentiation and specification of the stem cell-like seam cell lineages

摘要

TheRUNX/CBFβnbsp;heterodimerictranscriptionfactorplaysanimportantroleinregulatingcellproliferationanddifferentiationinavarietyofdevelopmentalcontexts.AberrantfunctionofRunxandCBFβhasbeencausallyrelatedtothedevelopmentofvariousdiseases,includingacutemyeloidleukemia,gastriccancerandcleidocranialdysplasia.TheunderlyingmechanismoftheRUNX/CBFβcomplexinregulationofcellproliferationisstillpoorlydefined.Inthisstudy,wedemonstratethattheemCaenorhabditiselegans/emCBFβhomolog,embro-1/em,isessentialfortheproliferation,differentiationandspecificationofarowofstemcell-likelineages,calledseamcells.BRO-1formscomplexwiththeemC.elegans/emRUNXhomolog,RNT-1,andaugmentstheDNA-bindingactivityofRNT-1.TheRNT-1/BRO-1complexdirectlyinteractswiththeemC.elegans/emGrouchohomolog,UNC-37,whoselossoffunctionmutationsdisplaysimilardefectsintheproliferationofseamcellsasthoseofembro-1/emandemrnt-1/emmutants.Additionally,thedefectsinseamcelldivisioninembro-1/emmutantsaresubstantiallyrescuedbytheinactivationofthenegativeregulatorsoftheG1toSphasecellcycleprogression,includingtheemlin-35/emRb,emfzr-1/emCdh1andemcki-1/emCIPhomologs.OurstudiesindicatethatthetranscriptionalrepressionactivityoftheRNT-1/BRO-1complexregulatestheG1toScellcycleprogressionduringseamcelldivision./p/div