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Chromatin immunoprecipitation of Foxp3 in mouse T-cell hybridoma cells

ABSTRACT: The forkhead transcription factor Foxp3 is essential for the development of CD4+CD25+ regulatory T (Treg) cells and prevention of autoimmunity, but how it controls the Treg gene expression program is not understood. We describe here genome-wide location and expression data that identify Foxp3 target genes and report that many Foxp3 target genes are key modulators of T cell activation and function. Remarkably, the predominant effect of Foxp3 binding is to suppress the activation of target genes upon T cell stimulation. Foxp3 suppression of its targets appears to be crucial for the normal function of Treg cells because overactive variants of some target genes are known to be associated with autoimmune disease.

ORGANISM(S): Mus musculus

SUBMITTER: Elizabeth Herbolsheimer

PROVIDER: E-TABM-154 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Foxp3 occupancy and regulation of key target genes during T-cell stimulation.

Marson Alexander A Kretschmer Karsten K Frampton Garrett M GM Jacobsen Elizabeth S ES Polansky Julia K JK MacIsaac Kenzie D KD Levine Stuart S SS Fraenkel Ernest E von Boehmer Harald H Young Richard A RA

Nature 20070121 7130

Foxp3+CD4+CD25+ regulatory T (T(reg)) cells are essential for the prevention of autoimmunity. T(reg) cells have an attenuated cytokine response to T-cell receptor stimulation, and can suppress the proliferation and effector function of neighbouring T cells. The forkhead transcription factor Foxp3 (forkhead box P3) is selectively expressed in T(reg) cells, is required for T(reg) development and function, and is sufficient to induce a T(reg) phenotype in conventional CD4+CD25- T cells. Mutations i ...[more]

PMID: 17237765

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