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Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells
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Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells
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Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells
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Journal Article
Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells
2014
Overview
The transcription factor Foxp3 is essential for the function of regulatory T cells (T
reg
cells). Rudensky and colleagues show binding of Foxp3 poises target genes for repression and, after activation of T
reg
cells, recruits the histone methyltransferase Ezh2.
The transcription factor Foxp3 is indispensable for the ability of regulatory T cells (T
reg
cells) to suppress fatal inflammation. Here we characterized the role of Foxp3 in chromatin remodeling and the regulation of gene expression in actively suppressive T
reg
cells in an inflammatory setting. Although genome-wide occupancy of regulatory elements in DNA by Foxp3 was similar in resting T
reg
cells and those activated
in vivo
, Foxp3-bound enhancer elements in the DNA were poised for repression only in activated T
reg
cells. Following activation, Foxp3-bound sites showed diminished accessibility of chromatin and selective deposition of histone H3 trimethylated at Lys27 (H3K27me3), which was associated with recruitment of the histone methyltransferase Ezh2 and downregulation of the expression of nearby genes. Thus, Foxp3 poises its targets for repression by facilitating the formation of repressive chromatin in T
reg
cells upon their activation in response to inflammatory cues.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 38
/ 38/61
/ 45/15
/ 45/23
/ 45/61
/ 45/77
/ 631/250
/ Animals
/ Chromatin Assembly and Disassembly
/ DNA
/ DNA Methylation - immunology
/ Enhancer of Zeste Homolog 2 Protein
/ Forkhead Transcription Factors - immunology
/ Gene Expression Regulation - immunology
/ Lymphocyte Activation - immunology
/ Mice
/ Polycomb Repressive Complex 2 - genetics
/ Polycomb Repressive Complex 2 - immunology
/ Receptors, Antigen, T-Cell - immunology
/ resource
/ Signal Transduction - immunology
/ T cells
