Transcription factor Foxp3 and its protein partners form a complex regulatory network.
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.
Mesh Terms:
Animals, Cell Differentiation, Forkhead Transcription Factors, GATA3 Transcription Factor, Gene Expression Regulation, Gene Regulatory Networks, Humans, Mice, Mice, Transgenic, Protein Structure, Tertiary, Proteomics, T-Lymphocytes, Regulatory
Animals, Cell Differentiation, Forkhead Transcription Factors, GATA3 Transcription Factor, Gene Expression Regulation, Gene Regulatory Networks, Humans, Mice, Mice, Transgenic, Protein Structure, Tertiary, Proteomics, T-Lymphocytes, Regulatory
Nat. Immunol.
Date: Oct. 01, 2012
PubMed ID: 22922362
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