The chromatin remodeler CHD8 governs hematopoietic stem/progenitor survival by regulating ATM-mediated P53 protein stability.

ABSTRACT: The Chd8 gene encodes a member of the chromodomain helicase DNA-binding (CHD) family of SNF2H-like adenosine triphosphate (ATP)-dependent chromatin remodeler, the mutations of which define a subtype of autism spectrum disorders. Increasing evidence from recent studies indicates that ATP-dependent chromatin-remodeling genes are involved in the control of crucial gene-expression programs in hematopoietic stem/progenitor cell (HSPC) regulation. In this study, we identified CHD8 as a specific and essential regulator of normal hematopoiesis. Loss of Chd8 leads to severe anemia, pancytopenia, bone marrow failure, and engraftment failure related to a drastic depletion of HSPCs. CHD8 forms a complex with ATM and its deficiency increases chromatin accessibility and drives genomic instability in HSP

SUBMITTER: Tu Z 

PROVIDER: S-EPMC8310427 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature