Histone H3K36 methyltransferases NSD1 and SETD2 are required for brain development.

Journal: Human Genetics
Published:
Abstract

Genetic variants in two major histone H3K36 methyltransferases, NSD1 and SETD2, have been identified in patients with neurodevelopmental disorders. We examined the genetic nature of these disease-relevant variants and studied genotype-phenotype correlations using publicly available patient cohorts. To further investigate roles of Nsd1 and Setd2 in brain development, we generated mouse models with conditional knockout of Nsd1 and Setd2 in neuroepithelial cells using the Sox1-cre. Our results showed that conditional Nsd1 knockout mice were viable but exhibited reduced brain size and thinning of neocortex, while Setd2 knockout led to neonatal death with intracerebral hemorrhage and vascular abnormalities. Together, our study demonstrates new roles of Nsd1 and Setd2 in brain development.

Authors
Bo Chen, Chenyang Zhang, Huanwen Rui, Dan Shen, Zhuxi Huang, Weijun Feng