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Cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors

Multipotent hematopoietic progenitors must acquire thymus-homing capacity to initiate T lymphocyte development. Despite its importance, the transcriptional program underlying this process remains elusive. Cbfβ forms transcription factor complexes with Runx proteins, and here we show that Cbfβ2, enco...

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Autores principales: Tenno, Mari, Kojo, Satoshi, Lawir, Divine-Fondzenyuy, Hess, Isabell, Shiroguchi, Katsuyuki, Ebihara, Takashi, Endo, Takaho A., Muroi, Sawako, Satoh, Rumi, Kawamoto, Hiroshi, Boehm, Thomas, Taniuchi, Ichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789415/
https://www.ncbi.nlm.nih.gov/pubmed/29343500
http://dx.doi.org/10.1084/jem.20171221
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author Tenno, Mari
Kojo, Satoshi
Lawir, Divine-Fondzenyuy
Hess, Isabell
Shiroguchi, Katsuyuki
Ebihara, Takashi
Endo, Takaho A.
Muroi, Sawako
Satoh, Rumi
Kawamoto, Hiroshi
Boehm, Thomas
Taniuchi, Ichiro
author_facet Tenno, Mari
Kojo, Satoshi
Lawir, Divine-Fondzenyuy
Hess, Isabell
Shiroguchi, Katsuyuki
Ebihara, Takashi
Endo, Takaho A.
Muroi, Sawako
Satoh, Rumi
Kawamoto, Hiroshi
Boehm, Thomas
Taniuchi, Ichiro
author_sort Tenno, Mari
collection PubMed
description Multipotent hematopoietic progenitors must acquire thymus-homing capacity to initiate T lymphocyte development. Despite its importance, the transcriptional program underlying this process remains elusive. Cbfβ forms transcription factor complexes with Runx proteins, and here we show that Cbfβ2, encoded by an RNA splice variant of the Cbfb gene, is essential for extrathymic differentiation of T cell progenitors. Furthermore, Cbfβ2 endows extrathymic progenitors with thymus-homing capacity by inducing expression of the principal thymus-homing receptor, Ccr9. This occurs via direct binding of Cbfβ2 to cell type–specific enhancers, as is observed in Rorγt induction during differentiation of lymphoid tissue inducer cells by activation of an intronic enhancer. As in mice, an alternative splicing event in zebrafish generates a Cbfβ2-specific mRNA, important for ccr9 expression. Thus, despite phylogenetically and ontogenetically variable sites of origin of T cell progenitors, their robust thymus-homing capacity is ensured by an evolutionarily conserved mechanism emerging from functional diversification of Runx transcription factor complexes by acquisition of a novel splice variant.
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spelling pubmed-57894152018-08-05 Cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors Tenno, Mari Kojo, Satoshi Lawir, Divine-Fondzenyuy Hess, Isabell Shiroguchi, Katsuyuki Ebihara, Takashi Endo, Takaho A. Muroi, Sawako Satoh, Rumi Kawamoto, Hiroshi Boehm, Thomas Taniuchi, Ichiro J Exp Med Research Articles Multipotent hematopoietic progenitors must acquire thymus-homing capacity to initiate T lymphocyte development. Despite its importance, the transcriptional program underlying this process remains elusive. Cbfβ forms transcription factor complexes with Runx proteins, and here we show that Cbfβ2, encoded by an RNA splice variant of the Cbfb gene, is essential for extrathymic differentiation of T cell progenitors. Furthermore, Cbfβ2 endows extrathymic progenitors with thymus-homing capacity by inducing expression of the principal thymus-homing receptor, Ccr9. This occurs via direct binding of Cbfβ2 to cell type–specific enhancers, as is observed in Rorγt induction during differentiation of lymphoid tissue inducer cells by activation of an intronic enhancer. As in mice, an alternative splicing event in zebrafish generates a Cbfβ2-specific mRNA, important for ccr9 expression. Thus, despite phylogenetically and ontogenetically variable sites of origin of T cell progenitors, their robust thymus-homing capacity is ensured by an evolutionarily conserved mechanism emerging from functional diversification of Runx transcription factor complexes by acquisition of a novel splice variant. The Rockefeller University Press 2018-02-05 /pmc/articles/PMC5789415/ /pubmed/29343500 http://dx.doi.org/10.1084/jem.20171221 Text en © 2018 Tenno et al. http://www.rupress.org/termshttps://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 (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
Tenno, Mari
Kojo, Satoshi
Lawir, Divine-Fondzenyuy
Hess, Isabell
Shiroguchi, Katsuyuki
Ebihara, Takashi
Endo, Takaho A.
Muroi, Sawako
Satoh, Rumi
Kawamoto, Hiroshi
Boehm, Thomas
Taniuchi, Ichiro
Cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors
title Cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors
title_full Cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors
title_fullStr Cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors
title_full_unstemmed Cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors
title_short Cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors
title_sort cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789415/
https://www.ncbi.nlm.nih.gov/pubmed/29343500
http://dx.doi.org/10.1084/jem.20171221
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