A Bach2-Cebp gene regulatory network for the commitment of multipotent hematopoietic progenitors [ChIP-seq]

The commitment of hematopoietic stem cells and multipotent progenitors (MPPs) can be tuned to reprogram their differentiation capacity to be biased toward myeloid cells in response to an infection. Bach2, which inhibits myeloid differentiation in common lymphoid progenitors, repressed a cohort of genes of myeloid function (myeloid genes) and activated those for lymphoid function (lymphoid genes) in MPPs. In addition, Bach2 repressed both Cebpb and its target Csf1, encoding C/EBPß and macrophage colony-stimulating factor (M-CSF), respectively, whereas C/EBPß repressed Bach2 and activated the M-CSF receptor gene Csf1r. Bach2 and C/EBPß bound to overlapping regulatory regions of their myeloid target genes, suggesting the presence of a gene regulatory network (GRN) with mutual repression and antagonistic, feed-forward regulation of myeloid genes. Lipopolysaccharide reduced the expression of Bach2, resulting in enhanced myeloid differentiation. Bach2 tunes the commitment of multipotent progenitors to myeloid and lymphoid lineages under both normal and infectious conditions. Overall design: Sarch of Bach2 target genes in progenitor cells