Genomics

Dataset Information

20

Genome-wide location analysis of Dnmt3a-mediated epigenetic regulation in murine postnatal subventricular zone (SVZ) neural stem cells (NSCs) [Agilent]


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 non-proximal 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 non-proximal promoter methylation promotes expression of these neurogenic genes by functionally antagonizing Polycomb repression. Thus, non-promoter DNA methylation by Dnmt3a may be utilized for maintaining active chromatin states of genes critical for development. Overall design: Chromatin extracted from wild-type (WT) or Dnmt3a-null (KO) SVZ NSCs was immunoprecipitated with indicated antibodies and analyzed by Agilent 244K extended promoter (-5.5kb to +2.5kb flanking transcription start sites) microarrays. Whole cell extract (WCE) was used as input controls for most experiments (IP/WCE). For other experiments, immunoprecipitated DNA from WT and KO NSCs was directly compared on the same microarrays (IP/IP).

INSTRUMENT(S): Agilent-014716 Mouse Promoter ChIP-on-Chip Set 244K, Microarray 1 of 2 (G4490A) (Feature Number version)

SUBMITTER: Yi Sun   

PROVIDER: GSE22474 | GEO | 2010-06-25

SECONDARY ACCESSION(S): PRJNA129269

REPOSITORIES: GEO

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Publications

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

Wu Hao H   Coskun Volkan V   Tao Jifang J   Xie Wei W   Ge Weihong W   Yoshikawa Kazuaki K   Li En E   Zhang Yi Y   Sun Yi Eve YE  

Science (New York, N.Y.) 20100701 5990


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 inter  ...[more]

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