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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.

Pubmed ID: 22922362

Authors

  • Rudra D
  • deRoos P
  • Chaudhry A
  • Niec RE
  • Arvey A
  • Samstein RM
  • Leslie C
  • Shaffer SA
  • Goodlett DR
  • Rudensky AY

Journal

Nature immunology

Publication Data

October 20, 2012

Associated Grants

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

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