Brain-specific deletion of histone variant H2A.z results in cortical neurogenesis defects and neurodevelopmental disorder.

ABSTRACT: Defects in neurogenesis alter brain circuit formations and may lead to neurodevelopmental disorders such as autism and schizophrenia. Histone H2A.z, a variant of histone H2A, plays critical roles in chromatin structure and epigenetic regulation, but its function and mechanism in brain development remain largely unknown. Here, we find that the deletion of H2A.z results in enhanced proliferation of neural progenitors but reduced neuronal differentiation. In addition, neurons in H2A.z knockout mice exhibit abnormal dendrites during brain development. Furthermore, H2A.zcKO mice exhibit serial behavioral deficits, such as decreased exploratory activity and impaired learning and memory. Mechanistically, H2A.z regulates embryonic neurogenesis by targeting Nkx2-4 through interaction with Setd2, th

SUBMITTER: Shen T 

PROVIDER: S-EPMC5861433 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature