DOI: 10.1101/gad.1463706. Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication

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

10.1101/gad.1463706

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

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.

Bibliography

EstÃ¨ve, P.-O., Chin, H. G., Smallwood, A., Feehery, G. R., Gangisetty, O., Karpf, A. R., Carey, M. F., & Pradhan, S. (2006). Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication. Genes & Development, 20(22), 3089â3103.

Authors 8

Pierre-Olivier Estève (first)
Hang Gyeong Chin (additional)
Andrea Smallwood (additional)
George R. Feehery (additional)
Omkaram Gangisetty (additional)
Adam R. Karpf (additional)
Michael F. Carey (additional)
Sriharsa Pradhan (additional)

References 58 Referenced 444

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Dates

Type	When
Created	18 years, 9 months ago (Nov. 3, 2006, 8:25 p.m.)
Deposited	3 years, 9 months ago (Nov. 16, 2021, noon)
Indexed	4 hours, 46 minutes ago (Aug. 29, 2025, 5:59 a.m.)
Issued	18 years, 9 months ago (Nov. 3, 2006)
Published	18 years, 9 months ago (Nov. 3, 2006)
Published Online	18 years, 9 months ago (Nov. 3, 2006)
Published Print	18 years, 9 months ago (Nov. 15, 2006)

Funders 0

None

BibTeX

@article{Est_ve_2006, title={Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication}, volume={20}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1463706}, DOI={10.1101/gad.1463706}, number={22}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Estève, Pierre-Olivier and Chin, Hang Gyeong and Smallwood, Andrea and Feehery, George R. and Gangisetty, Omkaram and Karpf, Adam R. and Carey, Michael F. and Pradhan, Sriharsa}, year={2006}, month=nov, pages={3089–3103} }

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    "0890-9369",
    "1549-5477"
  ],
  "subject": [],
  "container-title-short": "Genes Dev.",
  "published": {
    "date-parts": [
      [
        2006,
        11,
        3
      ]
    ]
  }
}