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

Authors
 Hyoung-Pyo Kim  ;  Warren J. Leonard 
Citation
 JOURNAL OF EXPERIMENTAL MEDICINE, Vol.204(7) : 1543-1551, 2007 
Journal Title
JOURNAL OF EXPERIMENTAL MEDICINE
ISSN
 0022-1007 
Issue Date
2007
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 also induces FoxP3 expression. Conversely, methylation of the CpG island, which decreases CREB binding or expression of dominant-negative CREB, decreases FoxP3 gene expression. Thus, T cell receptor-induced FoxP3 expression in T reg cells is controlled both by sequence-specific binding of CREB/ATF and by DNA methylation of a CpG island.
Files in This Item:
T200705164.pdf Download
DOI
10.1084/jem.20070109
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyoung Pyo(김형표) ORCID logo https://orcid.org/0000-0003-1441-8822
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96334
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