Early chromatin unfolding by RUNX1: a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program

摘要: At the cellular level, development progresses through successive regulatory states, each characterized by their specific gene expression profile. However, molecular mechanisms regulating first priming and then maintenance of within one developmental pathway are essentially unknown. The hematopoietic system represents a powerful experimental model to address these questions here we have focused on circuit playing central role in myelopoiesis: transcription factor PU.1, its target colony-stimulating-factor 1 receptor (Csf1r), key upstream regulators such as RUNX1. We find that during ontogeny, chromatin unfolding precedes establishment active histone marks formation stable complexes at Pu.1 locus show remodeling is mediated transient binding RUNX1 cis-elements. By contrast, reorganization Csf1r requires prior PU.1 together with binding. Once full program established, can be maintained without Our experiments therefore demonstrate how individual factors function differentiation stage-specific manner differentially affect initiation versus program.