CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation.

ABSTRACT: Regulatory T cells (T reg cells) are a population of CD4+ T cells that limit immune responses. FoxP3 is a master control transcription factor for development and function of these cells, but its regulation is poorly understood. We have identified a T cell receptor-responsive enhancer in the FoxP3 first intron that is dependent on a cyclic-AMP response element binding protein (CREB)/activating transcription factor (ATF) site overlapping a CpG island. Methylation of this island inversely correlates with CREB binding and FoxP3 expression. Interestingly, transforming growth factor-beta, which induces T reg cell formation, decreases methylation of the CpG island and increases FoxP3 expression. Similarly, inhibiting methylation with 5-azacytidine or knocking down the DNA methyltransferase Dnmt1

SUBMITTER: Kim HP 

PROVIDER: S-EPMC2118651 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature