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The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus

The transcription factor Ets1 contributes to the differentiation of CD8 lineage cells in the thymus, but how it does so is not understood. In this study, we demonstrate that Ets1 is required for the proper termination of CD4 expression during the differentiation of major histocompatability class 1 (...

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Autores principales: Zamisch, Monica, Tian, Linhua, Grenningloh, Roland, Xiong, Yumei, Wildt, Kathryn F., Ehlers, Marc, Ho, I-Cheng, Bosselut, Rémy
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806616/
https://www.ncbi.nlm.nih.gov/pubmed/19917777
http://dx.doi.org/10.1084/jem.20092024
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author Zamisch, Monica
Tian, Linhua
Grenningloh, Roland
Xiong, Yumei
Wildt, Kathryn F.
Ehlers, Marc
Ho, I-Cheng
Bosselut, Rémy
author_facet Zamisch, Monica
Tian, Linhua
Grenningloh, Roland
Xiong, Yumei
Wildt, Kathryn F.
Ehlers, Marc
Ho, I-Cheng
Bosselut, Rémy
author_sort Zamisch, Monica
collection PubMed
description The transcription factor Ets1 contributes to the differentiation of CD8 lineage cells in the thymus, but how it does so is not understood. In this study, we demonstrate that Ets1 is required for the proper termination of CD4 expression during the differentiation of major histocompatability class 1 (MHC I)–restricted thymocytes, but not for other events associated with their positive selection, including the initiation of cytotoxic gene expression, corticomedullary migration, or thymus exit. We further show that Ets1 promotes expression of Runx3, a transcription factor important for CD8 T cell differentiation and the cessation of Cd4 gene expression. Enforced Runx3 expression in Ets1-deficient MHC I–restricted thymocytes largely rescued their impaired Cd4 silencing, indicating that Ets1 is not required for Runx3 function. Finally, we document that Ets1 binds at least two evolutionarily conserved regions within the Runx3 gene in vivo, supporting the possibility that Ets1 directly contributes to Runx3 transcription. These findings identify Ets1 as a key player during CD8 lineage differentiation and indicate that it acts, at least in part, by promoting Runx3 expression.
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spelling pubmed-28066162010-05-23 The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus Zamisch, Monica Tian, Linhua Grenningloh, Roland Xiong, Yumei Wildt, Kathryn F. Ehlers, Marc Ho, I-Cheng Bosselut, Rémy J Exp Med Article The transcription factor Ets1 contributes to the differentiation of CD8 lineage cells in the thymus, but how it does so is not understood. In this study, we demonstrate that Ets1 is required for the proper termination of CD4 expression during the differentiation of major histocompatability class 1 (MHC I)–restricted thymocytes, but not for other events associated with their positive selection, including the initiation of cytotoxic gene expression, corticomedullary migration, or thymus exit. We further show that Ets1 promotes expression of Runx3, a transcription factor important for CD8 T cell differentiation and the cessation of Cd4 gene expression. Enforced Runx3 expression in Ets1-deficient MHC I–restricted thymocytes largely rescued their impaired Cd4 silencing, indicating that Ets1 is not required for Runx3 function. Finally, we document that Ets1 binds at least two evolutionarily conserved regions within the Runx3 gene in vivo, supporting the possibility that Ets1 directly contributes to Runx3 transcription. These findings identify Ets1 as a key player during CD8 lineage differentiation and indicate that it acts, at least in part, by promoting Runx3 expression. The Rockefeller University Press 2009-11-23 /pmc/articles/PMC2806616/ /pubmed/19917777 http://dx.doi.org/10.1084/jem.20092024 Text en © 2009 The Rockefeller University Press 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 Article
Zamisch, Monica
Tian, Linhua
Grenningloh, Roland
Xiong, Yumei
Wildt, Kathryn F.
Ehlers, Marc
Ho, I-Cheng
Bosselut, Rémy
The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus
title The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus
title_full The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus
title_fullStr The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus
title_full_unstemmed The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus
title_short The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus
title_sort transcription factor ets1 is important for cd4 repression and runx3 up-regulation during cd8 t cell differentiation in the thymus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806616/
https://www.ncbi.nlm.nih.gov/pubmed/19917777
http://dx.doi.org/10.1084/jem.20092024
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