Role of ATP-dependent chromatin remodelers in hematopoietic stem and progenitor cell maintenance.

Abstract

ATP-dependent chromatin remodeling factors utilize energy from ATP hydrolysis to modulate DNA-histone structures and regulate gene transcription. They are essential during hematopoiesis and for hematopoietic stem and progenitor cell (HSPC) function. This review discusses the recently unveiled roles of these chromatin remodelers in HSPC regulation, with an emphasis on the mechanism of chromodomain helicase DNA-binding (CHD) family members. Recent studies of ATP-dependent chromatin remodelers have revealed that individual CHD family members engage in distinct mechanisms in regulating HSPC cell fate. For example, CHD8 is required for HSPC survival by restricting both P53 transcriptional activity and protein stability in steady state hematopoiesis while the related CHD7 physically interacts with RUNX family transcription factor 1 (RUNX1) and suppresses RUNX1-induced expansion of HSPCs during blood development. Moreover, other CHD subfamily members such as CHD1/CHD2 and CHD3/CHD4, as well as the switch/sucrose non-fermentable, imitation SWI, and SWI2/SNF2 related (SWR) families of chromatin modulators, have also been found important for HSPC maintenance by distinct mechanisms. The expanding knowledge of ATP-dependent chromatin remodelers in hematopoiesis illustrates their respective critical roles in HSPC maintenance including the regulation of HSPC differentiation, survival, and self-renewal. Further studies are warranted to elucidate how different chromatin remodeling complexes are integrated in various HSPC cell fate decisions during steady-state and stress hematopoiesis.