Chromodomain Helicase DNA-binding 4 (CHD4) is required for B cell identity and lineage progression

B cell specification and identity are controlled by transcription factors and cytokine receptors that drive the expression of stage-specific transcriptomes during lineage progression. A key feature of these mechanisms is the repression of inappropriate transcription. Here, we utilized RNA-seq to demonstrate that chromodomain helicase DNA-binding protein 4 (CHD4), an ATPase/helicase subunit of Mi-2/NuRD chromatin remodeling complexes, is essential for B cell identity. In mice that lack CHD4 selectively in the B lineage, defects include developmental arrest at the early pro-B cell stage. While many pro-B-specific genes are expressed in the mutant cells, transcripts that are normally restricted to other tissues including pancreas and bone are expressed out of context. Moreover, CHD4-deficient pro-B cells do not proliferate in response to IL-7, exhibit greatly decreased utilization of distal VH segments and accumulate DNA damage. Together, our data confirm the importance of CHD4 and NuRD complexes for the generation of functional B cells. RNA-seq transcriptome analysis of three independent RNA samples each from wild type or Chd4 conditional knockout pro-B cells sorted as B220+CD43+CD24+BP1-IgM- bone marrow cells. Following analysis of RNA-seq, the mutant cell population was found to have increased enrichment of plasmacytoid dendritic cells. The data was not used in the publication, 'Arends, T, C Dege, A Bortnick, et al. CHD4 is essential for transcriptional repression and lineage progression in B lymphopoiesis. PNAS USA [Epub ahead of print]. (PMID: 31085655)'.