Runx proteins regulate Foxp3 expression

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Title: Runx proteins regulate Foxp3 expression
Authors: Bruno, L
Mazzarella, L
Hoogenkamp, M
Hertweck, A
Cobb, BS
Sauer, S
Hadjur, S
Leleu, M
Naoe, Y
Telfer, JC
Bonifer, C
Taniuchi, I
Fisher, AG
Merkenschlager, M
Item Type: Journal Article
Abstract: Runx proteins are essential for hematopoiesis and play an important role in T cell development by regulating key target genes, such as CD4 and CD8 as well as lymphokine genes, during the specialization of naive CD4 T cells into distinct T helper subsets. In regulatory T (T reg) cells, the signature transcription factor Foxp3 interacts with and modulates the function of several other DNA binding proteins, including Runx family members, at the protein level. We show that Runx proteins also regulate the initiation and the maintenance of Foxp3 gene expression in CD4 T cells. Full-length Runx promoted the de novo expression of Foxp3 during inducible T reg cell differentiation, whereas the isolated dominant-negative Runt DNA binding domain antagonized de novo Foxp3 expression. Foxp3 expression in natural T reg cells remained dependent on Runx proteins and correlated with the binding of Runx/core-binding factor β to regulatory elements within the Foxp3 locus. Our data show that Runx and Foxp3 are components of a feed-forward loop in which Runx proteins contribute to the expression of Foxp3 and cooperate with Foxp3 proteins to regulate the expression of downstream target genes.
Issue Date: 26-Oct-2009
Date of Acceptance: 17-Sep-2009
URI: http://hdl.handle.net/10044/1/71584
DOI: https://doi.org/10.1084/jem.20090226
ISSN: 0022-1007
Publisher: Rockefeller University Press
Start Page: 2329
End Page: 2337
Journal / Book Title: Journal of Experimental Medicine
Volume: 206
Issue: 11
Copyright Statement: © 2009 Bruno et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons .org/licenses/by-nc-sa/3.0/).
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: PO4050659629
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
ROR-GAMMA-T
HELPER TYPE-1 CELLS
TRANSCRIPTION
DIFFERENTIATION
REPRESSION
GENE
CD4
METHYLATION
COOPERATE
MTOR
Animals
Core Binding Factor Alpha 3 Subunit
Core Binding Factor alpha Subunits
Core Binding Factor beta Subunit
Feedback, Physiological
Forkhead Transcription Factors
Genes, Dominant
Mice
Protein Structure, Tertiary
T-Lymphocytes, Regulatory
Animals
Mice
Protein Structure, Tertiary
Genes, Dominant
T-Lymphocytes, Regulatory
Core Binding Factor alpha Subunits
Core Binding Factor beta Subunit
Core Binding Factor Alpha 3 Subunit
Forkhead Transcription Factors
Feedback, Physiological
Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
ROR-GAMMA-T
HELPER TYPE-1 CELLS
TRANSCRIPTION
DIFFERENTIATION
REPRESSION
GENE
CD4
METHYLATION
COOPERATE
MTOR
11 Medical and Health Sciences
Immunology
Publication Status: Published
Online Publication Date: 2009-10-19
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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