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

Dipayan Rudra; Paul Deroos; Ashutosh Chaudhry; Rachel E. Niec; Aaron Arvey; Robert M. Samstein; Christina Leslie; Scott A. Shaffer; David R. Goodlett; Alexander Y. Rudensky

doi:10.1038/ni.2402

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

Dipayan Rudra
, Paul Deroos
, Ashutosh Chaudhry
, Rachel E. Niec
, Aaron Arvey
, Robert M. Samstein
, Christina Leslie
, Scott A. Shaffer
, David R. Goodlett
, Alexander Y. Rudensky

Research output: Contribution to journal › Article › peer-review

393 Scopus citations

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.

Original language	English
Pages (from-to)	1010-1019
Number of pages	10
Journal	Nature Immunology
Volume	13
Issue number	10
DOIs	https://doi.org/10.1038/ni.2402
State	Published - Oct 2012
Externally published	Yes

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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 (Treg 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 Treg cell biology.",

author = "Dipayan Rudra and Paul Deroos and Ashutosh Chaudhry and Niec, \{Rachel E.\} and Aaron Arvey and Samstein, \{Robert M.\} and Christina Leslie and Shaffer, \{Scott A.\} and Goodlett, \{David R.\} and Rudensky, \{Alexander Y.\}",

note = "Funding Information: We thank S. Lee, A. Bravo, J. Herlihy and J. Gerard for help with the mouse colony management and technical assistance; I.-C. Ho (Harvard Medical School) for Gata3fl/fl mice, D. Littman (New York University) for Runx1 antibody, I. Taniuchi (RIKEN Research Center for Allergy and Immunology) for Cbfβ andtibody and K. Georgopoulos (Massachusetts General Hospital) for Ikzf1 and Ikzf3 antibodies. This work was supported by US National Institutes of Health R37 AI034206 grant and the Howard Hughes Medical Institute (A.Y.R.). D.R. was supported by Arthritis Foundation postdoctoral fellowship. A.C. is supported by the Irvington Institute Fellowship Program of the Cancer Research Institute. R.E.N. is supported by National Institutes of Health Medical Scientist Training Program grant GM07739 and National Institute of Neurological Disorders and Stroke grant 1F31NS073203-01. R.M.S. is supported by National Institutes of Health DK091968 and Medical Scientist Training Program GM07739 grants.",

year = "2012",

month = oct,

doi = "10.1038/ni.2402",

language = "English",

volume = "13",

pages = "1010--1019",

journal = "Nature Immunology",

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T1 - Transcription factor Foxp3 and its protein partners form a complex regulatory network

AU - Rudra, Dipayan

AU - Deroos, Paul

AU - Chaudhry, Ashutosh

AU - Niec, Rachel E.

AU - Arvey, Aaron

AU - Samstein, Robert M.

AU - Leslie, Christina

AU - Shaffer, Scott A.

AU - Goodlett, David R.

AU - Rudensky, Alexander Y.

N1 - Funding Information: We thank S. Lee, A. Bravo, J. Herlihy and J. Gerard for help with the mouse colony management and technical assistance; I.-C. Ho (Harvard Medical School) for Gata3fl/fl mice, D. Littman (New York University) for Runx1 antibody, I. Taniuchi (RIKEN Research Center for Allergy and Immunology) for Cbfβ andtibody and K. Georgopoulos (Massachusetts General Hospital) for Ikzf1 and Ikzf3 antibodies. This work was supported by US National Institutes of Health R37 AI034206 grant and the Howard Hughes Medical Institute (A.Y.R.). D.R. was supported by Arthritis Foundation postdoctoral fellowship. A.C. is supported by the Irvington Institute Fellowship Program of the Cancer Research Institute. R.E.N. is supported by National Institutes of Health Medical Scientist Training Program grant GM07739 and National Institute of Neurological Disorders and Stroke grant 1F31NS073203-01. R.M.S. is supported by National Institutes of Health DK091968 and Medical Scientist Training Program GM07739 grants.

PY - 2012/10

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N2 - The transcription factor Foxp3 is indispensible for the differentiation and function of regulatory T cells (Treg 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 Treg cell biology.

AB - The transcription factor Foxp3 is indispensible for the differentiation and function of regulatory T cells (Treg 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 Treg cell biology.

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JO - Nature Immunology

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

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