Oligodendrocyte precursor survival and differentiation requires chromatin remodeling by Chd7 and Chd8

Abstract

Significance Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in the adult brain and deregulation of OPC proliferation-differentiation balance results in either glioma formation or defective (re)myelination. Mutations in chromatin remodelers CHD7 and CHD8 are the cause of CHARGE syndrome and some autism spectrum disorders (ASD). Here we show that Chd7 protects OPCs from apoptosis by chromatin closing and gene repression of p53 , while Chd7 induces chromatin opening and gene activation of OPC-differentiation regulators. Chd7 is, however, dispensable for oligodendrocyte stage progression, consistent with Chd8 compensatory function, as suggested by their common chromatin-binding profiles, including ASD-risk–associated genes. Our results thus involve oligodendroglia in ASD and CHARGE and offer new avenues to understand and modulate CHD7/CHD8 functions in normal and pathological brain development.