Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Issuree PD

PROVIDER: S-EPMC6125341 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Issuree Priya D PD Day Kenneth K Au Christy C Raviram Ramya R Zappile Paul P Skok Jane A JA Xue Hai-Hui HH Myers Richard M RM Littman Dan R DR

Nature communications 20180905 1

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 DN ...[more]

PMID: 30185805

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

Publications

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

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