Stepwise Activation of Enhancer and Promoter Regions of the B Cell Commitment Gene Pax5 in Early Lymphopoiesis

摘要: Pax5 is an essential regulator of B cell identity and function. Here, we used transgenesis deletion mapping to identify a potent enhancer in intron 5 the locus. This combination with promoter region was sufficient recapitulate lymphoid expression Pax5. The silenced by DNA methylation embryonic stem cells, but became activated multipotent hematopoietic progenitors. It contained functional binding sites for transcription factors PU.1, IRF4, IRF8, NF-kappaB, suggesting that these regulators contribute sequential activation progenitors during development. In contrast, repressed Polycomb group proteins non-B cells only at onset pro-B development through induction chromatin remodeling factor EBF1. These experiments demonstrate stepwise early lymphopoiesis provide mechanistic insights into process commitment.