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PMID: 17085482 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication.

Genes & development ·Vol. 20 ·No. 22 ·2006-11-15 ·Pages 3089-103

Estève PO, Chin HG, Smallwood A, Feehery GR, Gangisetty O, Karpf AR, Carey MF, Pradhan S

Abstract

Chromatin methylation is necessary for stable repression of gene expression during mammalian development. During cell division, DNMT1 maintains the DNA methylation pattern of the newly synthesized daughter strand, while G9a methylates H3K9. Here, DNMT1 is shown to directly bind G9a both in vivo and in vitro and to colocalize in the nucleus during DNA replication. The complex of DNMT1 and G9a colocalizes with dimethylated H3K9 (H3K9me2) at replication foci. Similarly, another H3K9 histone methyltransferase, SUV39H1, colocalizes with DNMT1 on heterochromatic regions of the nucleoli exclusively before cell division. Both DNMT1 and G9a are loaded onto the chromatin simultaneously in a ternary complex with loading factor PCNA during chromatin replication. Small interfering RNA (siRNA) knockdown of DNMT1 impairs DNA methylation, G9a loading, and H3K9 methylation on chromatin and rDNA repeats, confirming DNMT1 as the primary loading factor. Additionally, the complex of DNMT1 and G9a led to enhanced DNA and histone methylation of in vitro assembled chromatin substrates. Thus, direct cooperation between DNMT1 and G9a provides a mechanism of coordinated DNA and H3K9 methylation during cell division.

MeSH Terms
Animals COS Cells Chlorocebus aethiops DNA (Cytosine-5-)-Methyltransferases/chemistry,metabolism DNA Methylation DNA Replication DNA, Ribosomal Spacer/metabolism HCT116 Cells HeLa Cells Heterochromatin/metabolism Histone Methyltransferases Histone-Lysine N-Methyltransferase/chemistry,metabolism Histones/metabolism Humans Jurkat Cells Methyltransferases/metabolism Models, Genetic Protein Binding Protein Methyltransferases Protein Transport Repressor Proteins/metabolism
Chemicals
DNA, Ribosomal Spacer Heterochromatin Histones Repressor Proteins SUV39H1 protein, human Histone Methyltransferases Methyltransferases Protein Methyltransferases DNA (Cytosine-5-)-Methyltransferases Histone-Lysine N-Methyltransferase
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Estève Pierre-Olivier
New England Biolabs, Ipswich, Massachusetts 01938, USA.
Chin Hang Gyeong
Smallwood Andrea
Feehery George R
Gangisetty Omkaram
Karpf Adam R
Carey Michael F
Pradhan Sriharsa
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1463706
Published
2006-11-15
Epub
2006-00-03
Pages
3089-103
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1635145
Subset
IM
Grants
NCI NIH HHS · R01 CA116674 · United States
NCI NIH HHS · R01 CA116674-02 · United States
NCI NIH HHS · R01 CA11674 · United States
External Links
PubMed source DOI: 10.1101/gad.1463706 PMC Full Text View journal details
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