title: Transcription factor Foxp3 and its protein partners form a complex regulatory network.
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.
authors.affiliation: Howard Hughes Medical Institute and Immunology Program, Sloan-Kettering Institute, New York, New York, USA.
authors.forename: Dipayan
authors.initials: D
authors.lastname: Rudra
authors.forename: Paul
authors.initials: P
authors.lastname: deRoos
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chaudhry
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Niec
authors.forename: Aaron
authors.initials: A
authors.lastname: Arvey
authors.forename: Robert M
authors.initials: RM
authors.lastname: Samstein
authors.forename: Christina
authors.initials: C
authors.lastname: Leslie
authors.forename: Scott A
authors.initials: SA
authors.lastname: Shaffer
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Rudensky
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017434:Protein Structure, Tertiary; D040901:Proteomics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor