Autism-associated chromatin remodeler CHD8 regulates erythroblast cytokinesis and fine-tunes the balance of Rho GTPase signaling.

ABSTRACT: CHD8 is an ATP-dependent chromatin-remodeling factor whose monoallelic mutation defines a subtype of autism spectrum disorders (ASDs). Previous work found that CHD8 is required for the maintenance of hematopoiesis by integrating ATM-P53-mediated survival of hematopoietic stem/progenitor cells (HSPCs). Here, by using Chd8^F/FMx1-Cre combined with a Trp53^F/F mouse model that suppresses apoptosis of Chd8^-/- HSPCs, we identify CHD8 as an essential regulator of erythroid differentiation. Chd8^-/-P53^-/- mice exhibited severe anemia conforming to congenital dyserythropoietic anemia (CDA) phenotypes. Loss of CHD8 leads to drastically decreased numbers of orthochromatic erythroblasts and increased binucleated and multinucleated basophilic erythro

SUBMITTER: Tu Z 

PROVIDER: S-EPMC9302451 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature