DCAF7 regulates hematopoietic stem cell function and differentiation through polycomb repressive complex 1 (PRC1) modulation

Using a conditional knockout mouse model, we discovered that the absence of DCAF7 leads to accumulation of differentiating progenitors in the bone marrow, and impaired self-renewal capacity of HSCs. Furthermore, loss of Dcaf7 accelerates the differentiation of HSCs into the myeloid lineage.

At the molecular level, DCAF7 interacts with components of the polycomb repressive complex 1 (PRC1) and promotes their assembly into large macromolecular complexes. Chromatin profiling revealed that loss of DCAF7 leads to increased localization of RING1B at transcriptionally active genomic loci. This increased binding was observed at genes involved in myeloid differentiation and was associated with increased mRNA expression.