Transcription Factor Foxp3 and Its Protein Partners Form a Complex Regulatory Network

Overview

Journal Nat Immunol

Date 2012 Aug 28

PMID 22922362

Citations 254

Authors

Dipayan Rudra

Paul deRoos

Ashutosh Chaudhry

Rachel E Niec

Aaron Arvey

Robert M Samstein

Christina Leslie

Scott A Shaffer

David R Goodlett

Alexander Y Rudensky

Affiliations

Soon will be listed here.

Abstract

The transcription factor Foxp3 is indispensible for the differentiation and function of regulatory T cells (T(reg) cells). To gain insights into the molecular mechanisms of Foxp3-mediated gene expression, we purified Foxp3 complexes and explored their composition. Biochemical and mass-spectrometric analyses revealed that Foxp3 forms multiprotein complexes of 400-800 kDa or larger and identified 361 associated proteins, ∼30% of which were transcription related. Foxp3 directly regulated expression of a large proportion of the genes encoding its cofactors. Some transcription factor partners of Foxp3 facilitated its expression. Functional analysis of the cooperation of Foxp3 with one such partner, GATA-3, provided additional evidence for a network of transcriptional regulation afforded by Foxp3 and its associates to control distinct aspects of T(reg) cell biology.

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