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Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription
The role of AP-1 transcription factors in early B cell development and function is still incompletely characterized. Here we address the role of Fra-2 in B cell differentiation. Deletion of Fra-2 leads to impaired B cell proliferation in the bone marrow. In addition, IL-7–stimulated pro–B cell cultu...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502419/ https://www.ncbi.nlm.nih.gov/pubmed/28566276 http://dx.doi.org/10.1084/jem.20160514 |
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author | Ubieta, Kenia Garcia, Mireia Grötsch, Bettina Uebe, Steffen Weber, Georg F. Stein, Merle Ekici, Arif Schett, Georg Mielenz, Dirk Bozec, Aline |
author_facet | Ubieta, Kenia Garcia, Mireia Grötsch, Bettina Uebe, Steffen Weber, Georg F. Stein, Merle Ekici, Arif Schett, Georg Mielenz, Dirk Bozec, Aline |
author_sort | Ubieta, Kenia |
collection | PubMed |
description | The role of AP-1 transcription factors in early B cell development and function is still incompletely characterized. Here we address the role of Fra-2 in B cell differentiation. Deletion of Fra-2 leads to impaired B cell proliferation in the bone marrow. In addition, IL-7–stimulated pro–B cell cultures revealed a reduced differentiation from large pre–B cells to small B cells and immature B cells. Gene profiling and chromatin immunoprecipitation sequencing analyses unraveled a transcriptional reduction of the transcription factors Foxo1, Irf4, Ikaros, and Aiolos in Fra-2–deficient B cells. Moreover, expression of IL7Rα and Rag 1/2, downstream targets of Irf4 and Foxo1, were also reduced in the absence of Fra-2. Pro–B cell proliferation and small pre–B cell differentiation were fully rescued by expression of Foxo1 and Irf4 in Fra-2–deficient pro–B cells. Hence, Fra-2 is a key upstream regulator of Foxo1 and Irf4 expression and influences proliferation and differentiation of B cells at multiple stages. |
format | Online Article Text |
id | pubmed-5502419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-55024192018-01-03 Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription Ubieta, Kenia Garcia, Mireia Grötsch, Bettina Uebe, Steffen Weber, Georg F. Stein, Merle Ekici, Arif Schett, Georg Mielenz, Dirk Bozec, Aline J Exp Med Research Articles The role of AP-1 transcription factors in early B cell development and function is still incompletely characterized. Here we address the role of Fra-2 in B cell differentiation. Deletion of Fra-2 leads to impaired B cell proliferation in the bone marrow. In addition, IL-7–stimulated pro–B cell cultures revealed a reduced differentiation from large pre–B cells to small B cells and immature B cells. Gene profiling and chromatin immunoprecipitation sequencing analyses unraveled a transcriptional reduction of the transcription factors Foxo1, Irf4, Ikaros, and Aiolos in Fra-2–deficient B cells. Moreover, expression of IL7Rα and Rag 1/2, downstream targets of Irf4 and Foxo1, were also reduced in the absence of Fra-2. Pro–B cell proliferation and small pre–B cell differentiation were fully rescued by expression of Foxo1 and Irf4 in Fra-2–deficient pro–B cells. Hence, Fra-2 is a key upstream regulator of Foxo1 and Irf4 expression and influences proliferation and differentiation of B cells at multiple stages. The Rockefeller University Press 2017-07-03 /pmc/articles/PMC5502419/ /pubmed/28566276 http://dx.doi.org/10.1084/jem.20160514 Text en © 2017 Ubieta et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Ubieta, Kenia Garcia, Mireia Grötsch, Bettina Uebe, Steffen Weber, Georg F. Stein, Merle Ekici, Arif Schett, Georg Mielenz, Dirk Bozec, Aline Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription |
title | Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription |
title_full | Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription |
title_fullStr | Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription |
title_full_unstemmed | Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription |
title_short | Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription |
title_sort | fra-2 regulates b cell development by enhancing irf4 and foxo1 transcription |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502419/ https://www.ncbi.nlm.nih.gov/pubmed/28566276 http://dx.doi.org/10.1084/jem.20160514 |
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