Runx proteins regulate Foxp3 expression
File(s)
Published version
Author(s)
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.
Date Issued
2009-10-26
Date Acceptance
2009-09-17
Citation
Journal of Experimental Medicine, 2009, 206 (11), pp.2329-2337
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/).
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
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000271164000005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
PO4050659629
Subjects
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
Publication Status
Published
Date Publish Online
2009-10-19