%0 Journal Article
%T Cbf¦Â2 controls differentiation of and confers homing capacity to prethymic progenitors
%J JEM | The Journal of Experimental Medicine
%D 2018
%R 10.1084/jem.20171221
%X Multipotent hematopoietic progenitors must acquire thymus-homing capacity to initiate T lymphocyte development. Despite its importance, the transcriptional program underlying this process remains elusive. Cbf¦Â forms transcription factor complexes with Runx proteins, and here we show that Cbf¦Â2, encoded by an RNA splice variant of the Cbfb gene, is essential for extrathymic differentiation of T cell progenitors. Furthermore, Cbf¦Â2 endows extrathymic progenitors with thymus-homing capacity by inducing expression of the principal thymus-homing receptor, Ccr9. This occurs via direct binding of Cbf¦Â2 to cell type¨Cspecific enhancers, as is observed in Ror¦Ãt 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 Cbf¦Â2-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.
%U http://jem.rupress.org/content/215/2/595