Bcl11b-Cxxc1 axis regulates stage-specific chromatin accessibility during thymocyte development [ChIP-seq]

A mouse strain expressing a truncated form of Bcl11b lacking the C-terminal ZnF exhibited a dusrpted chromatin accessibility in CD4+CD8+ double-positive thymocytes. A comprehensive screen of chromatin modifiers associated with the C-terminal ZnF in Bcl11b identified Cxxc1, a protein known to mediate H3K4me3 as a component of Set1 complex.

Cxxc1-deficiency caused a developmental arrest at the transition from CD4-CD8- double-negaitve to CD4+CD8+ double-positive thymocytes, leading to the retention of a double-negative-like chromatin structure in double-positive cells and ectopic expression of double-negative signature genes. Genomic regions bound by Cxxc1 largely overlapped with Bcl11b binding sites, and were altered upon loss of Bcl11b. Consistent with the interaction between Cxxc1 and another Bcl11 family protein, Bcl11a―which is essential for B-lymphopoiesis―Cxxc1-deficiency caused a developmental arrest of B lymphocyte at the transition from BP-1- to BP-1+ stage.