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

Nature immunology | Oct 20, 2012

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.

Pubmed ID: 22922362 RIS Download

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

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Associated grants

  • Agency: NIGMS NIH HHS, Id: GM07739
  • Agency: NINDS NIH HHS, Id: F31 NS073203
  • Agency: NINDS NIH HHS, Id: 1F31NS073203-01
  • Agency: NIDDK NIH HHS, Id: DK091968
  • Agency: NIAID NIH HHS, Id: R37 AI034206
  • Agency: Howard Hughes Medical Institute, Id: F30 DK091968
  • Agency: NIDDK NIH HHS, Id: T32 GM007739
  • Agency: NIGMS NIH HHS, Id:

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