Genome-wide maps of Cbfb variants bound regions in E12.5 lineage negative fetal liver cells and adult thymocytes.

Multi-potent hematopietic progenitors must acquire thymus-homing capacity to initiate T lymphocyte development. Despite its importance, the transcriptional program underlying this process remains elusive. Cbfß forms transcription factor complexes with Runx proteins, and here we sho that Cbfß2, encoded by an RNA splice variant of the Cbfb gene, is essential for differentiation of IL7R+PIRhi thymic-homing progenitors in the mouse fetal liver. Cbfß2 binds to cell-type specific enhancers and induces expression of the principal thymus-homing receptor CCR9. Like in mouse, an alternative splicing event generates Cbfß2-specific mRNA whose products controls CCR9 expression and thymus homing in zebrafish. Our findings indicate that functional diversification of Runx transcription factor complexes via alternative splicing emerged early in evolution to support a key step in T cell development. Overall design: Sequencing of Cbfb ChIP-seq from E12.5 lineage negative fetal liver cells and adult thymocytes.