The histone deacetylase HDAC7 represses lineage-inappropriate genes and is essential for proper B cell generation

B lymphocyte development is a complex process tightly controlled at the transcriptional level by the action of networks of transcription factors. The repression of genes from alternative lineages is necessary to ensure the acquisition of the correct B cell identity. However, the mechanisms of transcriptional repression during B cell generation are largely unknown. Here, using a conditional knockout mouse model, we show that the histone deacetylase HDAC7 is essential for B cell development. Early deletion of HDAC7 dramatically blocked B cell development at the pro-B cell stage and gave rise to a severe lymphopenia in peripheral organs. HDAC7-deficient pro-B cells exhibit cell lineage promiscuity, expressing myeloid and T lymphocyte genes. In wild-type B cells HDAC7 is recruited to myocyte enhancer factor 2C (MEFC2) binding sites located at the promoters of macrophage and T lymphocyte genes. Our results demonstrate that HDAC7 is a bona fide transcriptional repressor essential for B cell development. Biological triplicates of pro-B cells purified from wild-type and HDAC7 conditional mice. Total RNA from purified pro-B cells was extracted by Trizol. PCR amplified RNAs were hybridized against Affymetrix mouse arrays chip (Mouse Genome 430 PM strip)