In vivo conditional deletion of HDAC7 reveals its requirement to establish proper B lymphocyte identity and development

Class IIa Histone Deacetylases (HDACs) subfamily members are tissue-specific gene repressors with crucial roles in development and differentiation processes. A prominent example is HDAC7, a class IIa HDAC that shows a lymphoid-specific expression pattern within the hematopoietic system. Here, we explored its potential role in B cell development by generating a conditional knockout mouse model. Our study demonstrates for the first time that HDAC7 deletion dramatically blocks early B cell development and gives rise to a severe lymphopenia in peripheral organs, while leading to pro-B cell lineage promiscuity. We find that HDAC7 represses myeloid and T lymphocyte genes in B cell progenitors, through interaction with myocyte enhancer factor 2C (MEFC2). We performed ChIP-seq assays using purified pro-B cells from wild type and HDAC7-deficient mice. We observed an enrichment of H3K9/14Ac at the promoters of myeloid and T cell genes in both wild type and HDAC7-deficient pro-B cells. Our results prove that HDAC7 is a bona fide transcriptional repressor essential for B cell development.