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Nature Research, Nature Immunology, 10(13), p. 1010-1019, 2012

DOI: 10.1038/ni.2402

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Transcription factor Foxp3 and its protein partners form a complex regulatory network

Journal article published in 2012 by Dipayan Rudra, Paul deRoos, Ashutosh Chaudhry, Rachel E. Niec ORCID, Aaron Arvey, Robert M. Samstein ORCID, Christina Leslie, Scott A. Shaffer, David R. Goodlett, Alexander Y. Rudensky
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.