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

Nat Immunol. 2012 Oct;13(10):1010-9. doi: 10.1038/ni.2402. Epub 2012 Aug 26.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism
  • Gene Expression Regulation*
  • Gene Regulatory Networks*
  • Humans
  • Mice
  • Mice, Transgenic
  • Protein Structure, Tertiary
  • Proteomics
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • GATA3 Transcription Factor

Associated data

  • GEO/GSE39864