Cbfβ2 controls differentiation of and confers homing capacity to prethymic progenitors : = Cbf[beta]2 controls differentiation of and confers homing capacity to prethymic progenitors

Abstract: 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

Weitere Titel
Cbf[beta]2 controls differentiation of and confers homing capacity to prethymic progenitors
Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Journal of experimental medicine : JEM. - 215, 2 (2018) , 595-610, ISSN: 1540-9538

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2019
Urheber
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

DOI
10.1084/jem.20171221
URN
urn:nbn:de:bsz:25-freidok-1479677
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
25.03.2025, 13:44 MEZ

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  • 2019

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