Format

Send to

Choose Destination
Science. 2010 Jul 23;329(5990):444-8. doi: 10.1126/science.1190485.

Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes.

Author information

1
Department of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA. haowu7@gmail.com

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.

PMID:
20651149
PMCID:
PMC3539760
DOI:
10.1126/science.1190485
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center