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

D Rudra, P Deroos, A Chaudhry, RE Niec, A Arvey… - Nature …, 2012 - nature.com
D Rudra, P Deroos, A Chaudhry, RE Niec, A Arvey, RM Samstein, C Leslie, SA Shaffer
Nature immunology, 2012nature.com
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 …
Abstract
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.
nature.com