Dnmt3a-dependent Nonpromoter DNA Methylation Facilitates Transcription of Neurogenic Genes

Overview

Journal Science

Specialty Science

Date 2010 Jul 24

PMID 20651149

Citations 332

Authors

Hao Wu

Volkan Coskun

Jifang Tao

Wei Xie

Weihong Ge

Kazuaki Yoshikawa

En Li

Yi Zhang

Yi Eve Sun

Affiliations

Soon will be listed here.

Abstract

DNA methylation at proximal promoters facilitates lineage restriction by silencing cell type-specific genes. However, euchromatic DNA methylation frequently occurs in regions outside promoters. The functions of such nonproximal promoter DNA methylation are unclear. Here we show that the de novo DNA methyltransferase Dnmt3a is expressed in postnatal neural stem cells (NSCs) and is required for neurogenesis. Genome-wide analysis of postnatal NSCs indicates that Dnmt3a occupies and methylates intergenic regions and gene bodies flanking proximal promoters of a large cohort of transcriptionally permissive genes, many of which encode regulators of neurogenesis. Surprisingly, Dnmt3a-dependent nonproximal promoter methylation promotes expression of these neurogenic genes by functionally antagonizing Polycomb repression. Thus, nonpromoter DNA methylation by Dnmt3a may be used for maintaining active chromatin states of genes critical for development.

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