Transcription factor Foxp3 and its protein partners form a complex regulatory network
2012; Nature Portfolio; Volume: 13; Issue: 10 Linguagem: Inglês
10.1038/ni.2402
ISSN1529-2916
AutoresDipayan Rudra, Paul deRoos, Ashutosh Chaudhry, Rachel Niec, Aaron Arvey, Robert M. Samstein, Christina Leslie, Scott A. Shaffer, David R. Goodlett, Alexander Y. Rudensky,
Tópico(s)Immunotherapy and Immune Responses
ResumoThe transcription factor Foxp3 is essential for the function of regulatory T cells. Rudensky and colleagues show Foxp3 participates in large protein complexes that regulate gene expression of many of these components in self-reinforcing networks. The transcription factor Foxp3 is indispensible for the differentiation and function of regulatory T cells (Treg 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 Treg cell biology.
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