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Runx proteins regulate Foxp3 expression

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...

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Autores principales: Bruno, Ludovica, Mazzarella, Luca, Hoogenkamp, Maarten, Hertweck, Arnulf, Cobb, Bradley S., Sauer, Stephan, Hadjur, Suzana, Leleu, Marion, Naoe, Yoshinori, Telfer, Janice C., Bonifer, Constanze, Taniuchi, Ichiro, Fisher, Amanda G., Merkenschlager, Matthias
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768863/
https://www.ncbi.nlm.nih.gov/pubmed/19841090
http://dx.doi.org/10.1084/jem.20090226
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author Bruno, Ludovica
Mazzarella, Luca
Hoogenkamp, Maarten
Hertweck, Arnulf
Cobb, Bradley S.
Sauer, Stephan
Hadjur, Suzana
Leleu, Marion
Naoe, Yoshinori
Telfer, Janice C.
Bonifer, Constanze
Taniuchi, Ichiro
Fisher, Amanda G.
Merkenschlager, Matthias
author_facet Bruno, Ludovica
Mazzarella, Luca
Hoogenkamp, Maarten
Hertweck, Arnulf
Cobb, Bradley S.
Sauer, Stephan
Hadjur, Suzana
Leleu, Marion
Naoe, Yoshinori
Telfer, Janice C.
Bonifer, Constanze
Taniuchi, Ichiro
Fisher, Amanda G.
Merkenschlager, Matthias
author_sort Bruno, Ludovica
collection PubMed
description 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.
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spelling pubmed-27688632010-04-26 Runx proteins regulate Foxp3 expression Bruno, Ludovica Mazzarella, Luca Hoogenkamp, Maarten Hertweck, Arnulf Cobb, Bradley S. Sauer, Stephan Hadjur, Suzana Leleu, Marion Naoe, Yoshinori Telfer, Janice C. Bonifer, Constanze Taniuchi, Ichiro Fisher, Amanda G. Merkenschlager, Matthias J Exp Med Brief Definitive Report 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. The Rockefeller University Press 2009-10-26 /pmc/articles/PMC2768863/ /pubmed/19841090 http://dx.doi.org/10.1084/jem.20090226 Text en © 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/).
spellingShingle Brief Definitive Report
Bruno, Ludovica
Mazzarella, Luca
Hoogenkamp, Maarten
Hertweck, Arnulf
Cobb, Bradley S.
Sauer, Stephan
Hadjur, Suzana
Leleu, Marion
Naoe, Yoshinori
Telfer, Janice C.
Bonifer, Constanze
Taniuchi, Ichiro
Fisher, Amanda G.
Merkenschlager, Matthias
Runx proteins regulate Foxp3 expression
title Runx proteins regulate Foxp3 expression
title_full Runx proteins regulate Foxp3 expression
title_fullStr Runx proteins regulate Foxp3 expression
title_full_unstemmed Runx proteins regulate Foxp3 expression
title_short Runx proteins regulate Foxp3 expression
title_sort runx proteins regulate foxp3 expression
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768863/
https://www.ncbi.nlm.nih.gov/pubmed/19841090
http://dx.doi.org/10.1084/jem.20090226
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