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

Priya D IssureeKenneth DayChristy AuRamya RaviramPaul ZappileJane A SkokHai-Hui XueRichard M MyersDan R Littman
Published in: Nature communications (2018)
The inheritance of gene expression patterns is dependent on epigenetic regulation, but the establishment and maintenance of epigenetic landscapes during T cell differentiation are incompletely understood. Here we show that two stage-specific Cd4 cis-elements, the previously characterized enhancer E4p and a novel enhancer E4m, coordinately promote Cd4 transcription in mature thymic MHC-II-specific T cells, in part through the canonical Wnt pathway. Specifically, E4p licenses E4m to orchestrate DNA demethylation by TET1 and TET3, which in turn poises the Cd4 locus for transcription in peripheral T cells. Cd4 locus demethylation is important for subsequent Cd4 transcription in activated peripheral T cells wherein these cis-elements become dispensable. By contrast, in developing thymocytes the loss of TET1/3 does not affect Cd4 transcription, highlighting an uncoupled event between transcription and epigenetic modifications. Together our findings reveal an important function for thymic cis-elements in governing gene expression in the periphery via a heritable epigenetic mechanism.
Keyphrases
  • gene expression
  • transcription factor
  • dna methylation
  • nk cells
  • binding protein
  • stem cells
  • magnetic resonance imaging
  • cell free
  • copy number
  • long non coding rna
  • quantum dots
  • circulating tumor
  • single molecule