The Bcl11–Cxxc1 axis regulates stage-specific chromatin accessibility during lymphocyte development

A zinc finger transcription factor, Bcl11b, is crucial for T-lymphopoiesis. A truncated Bcl11b lacking the C-terminal zinc finger disrupts chromatin accessibility in CD4 + CD8 + double-positive thymocytes. Screening chromatin modifiers associated with this zinc finger identified Cxxc1, a component of the Set1 complex mediating H3K4me3. Cxxc1 deficiency arrests the CD4 − CD8 − double-negative-to-double-positive transition, retaining double-negative-like chromatin structure in double-positive thymocytes. Genomic regions bound by Cxxc1 largely overlapped with Bcl11b and were altered upon Bcl11b deficiency. Similar effects are observed in B-lymphocytes via another Bcl11 family protein, Bcl11a, highlighting the role of Bcl11 family proteins in recruiting Cxxc1 in chromatin modulation during lymphopoiesis.