CBX8, a component of the Polycomb PRC1 complex, modulates DOT1L‐mediated gene expression through AF9/MLLT3

摘要

AF9isknowntointeractwithmultipleproteinsincludingactivatorsandrepressorsoftranscription.OurdataindicatethatotherAF9bindingproteinscompetewiththehistonemethyltransferaseDOT1LforAF9bindingthusdiminishingitsabilitytomethylatelysine79ofhistone3.Specifically,weshowthatAF9ispartofaproteinmultimercontainingmembersofPolycombgroup(PcG)PRC1complex,CBX8,RING1B,andBMI1.InteractionwithCBX8precludesAF9–DOT1Lbinding.KnockdownofCBX8withshort‐hairpinRNA(shRNA)leadstodecreasedexpressionoftheAF9targetgeneENaCα.Incontrast,CBX8overexpressionresultsinincreasedENaCαmRNAlevelsandthiseffectcanbepartiallyovercomebyco‐overexpressionofAF9...