Stage-specific epigenetic regulation of CD4 expression by coordinated enhancer elements during T cell development.

摘要: The inheritance of gene expression patterns is dependent on epigenetic regulation, but the establishment and maintenance landscapes during T cell differentiation are incompletely understood. Here we show that two stage-specific Cd4 cis-elements, previously characterized enhancer E4p a novel E4m, coordinately promote transcription in mature thymic MHC-II-specific cells, part through canonical Wnt pathway. Specifically, licenses E4m to orchestrate DNA demethylation by TET1 TET3, which turn poises locus for peripheral cells. important subsequent activated cells wherein these cis-elements become dispensable. By contrast, developing thymocytes loss TET1/3 does not affect transcription, highlighting an uncoupled event between modifications. Together our findings reveal function governing periphery via heritable mechanism.