Open AccessDnmt3a-Dependent Nonpromoter DNA Methylation Facilitates Transcription of Neurogenic Genes
Author(s) -
Hao Wu,
Volkan Coskun,
Jifang Tao,
Wei Xie,
Weihong Ge,
Kunio Yoshikawa,
En Li,
Yi Zhang,
Yi Sun
Publication year - 2010
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.1190485
Subject(s) - dna methylation , biology , promoter , epigenetics of physical exercise , rna directed dna methylation , methylation , gene , chromatin , genetics , neurogenesis , microbiology and biotechnology , gene expression
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.