Chromatin reader Dido3 regulates the genetic network of B cell differentiation

The development of hematopoietic lineages is based on a complex balance of transcription factors whose expression depends on the epigenetic signatures that characterize each differentiation step. The B cell lineage arises from hematopoietic stem cells through the stepwise silencing of stemness genes and balanced expression of mutually regulated transcription factors, as well as DNA rearrangement. Here we report the impact on B cell differentiation of lack of Dido3, a reader of the chromatin status, in the hematopoietic compartment. We found a reduced DNA accessibility in hematopoietic precursors, leading to severe deficiency in the generation of successive B cell differentiation stages. The expression of essential transcription factors and differentiation markers is affected, as is the somatic recombination process. Overall design: List of chromatin accessibility regions and mRNA profiles of DIDO3 wild type and mutants in mouse hematopoietic precursors