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Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation.

Publication ,  Journal Article
Ren, W; Fan, H; Grimm, SA; Guo, Y; Kim, JJ; Yin, J; Li, L; Petell, CJ; Tan, X-F; Zhang, Z-M; Coan, JP; Gao, L; Cai, L; Detrick, B; Çetin, B ...
Published in: Proc Natl Acad Sci U S A
August 4, 2020
Published version (DOI) Link to item

In mammals, repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3), frequently coexist with DNA methylation, producing a more stable and silenced chromatin state. However, it remains elusive how these epigenetic modifications crosstalk. Here, through structural and biochemical characterizations, we identified the replication foci targeting sequence (RFTS) domain of maintenance DNA methyltransferase DNMT1, a module known to bind the ubiquitylated H3 (H3Ub), as a specific reader for H3K9me3/H3Ub, with the recognition mode distinct from the typical trimethyl-lysine reader. Disruption of the interaction between RFTS and the H3K9me3Ub affects the localization of DNMT1 in stem cells and profoundly impairs the global DNA methylation and genomic stability. Together, this study reveals a previously unappreciated pathway through which H3K9me3 directly reinforces DNMT1-mediated maintenance DNA methylation.

Duke Scholars

G. Greg Wang
Author G. Greg Wang Pharmacology & Cancer Biology
Yiran Guo
Author Yiran Guo  

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.2009316117

EISSN

1091-6490

Publication Date

August 4, 2020

Volume

117

Issue

31

Start / End Page

18439 / 18447

Location

United States

Related Subject Headings

  • Protein Processing, Post-Translational
  • Methylation
  • Lysine
  • Humans
  • Histones
  • Heterochromatin
  • DNA Methylation
  • DNA (Cytosine-5-)-Methyltransferase 1
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ren, W., Fan, H., Grimm, S. A., Guo, Y., Kim, J. J., Yin, J., … Song, J. (2020). Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation. Proc Natl Acad Sci U S A, 117(31), 18439–18447. https://doi.org/10.1073/pnas.2009316117
Ren, Wendan, Huitao Fan, Sara A. Grimm, Yiran Guo, Jae Jin Kim, Jiekai Yin, Linhui Li, et al. “Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation.” Proc Natl Acad Sci U S A 117, no. 31 (August 4, 2020): 18439–47. https://doi.org/10.1073/pnas.2009316117.
Ren W, Fan H, Grimm SA, Guo Y, Kim JJ, Yin J, et al. Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation. Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18439–47.
Ren, Wendan, et al. “Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation.” Proc Natl Acad Sci U S A, vol. 117, no. 31, Aug. 2020, pp. 18439–47. Pubmed, doi:10.1073/pnas.2009316117.
Ren W, Fan H, Grimm SA, Guo Y, Kim JJ, Yin J, Li L, Petell CJ, Tan X-F, Zhang Z-M, Coan JP, Gao L, Cai L, Detrick B, Çetin B, Cui Q, Strahl BD, Gozani O, Wang Y, Miller KM, O’Leary SE, Wade PA, Patel DJ, Wang GG, Song J. Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation. Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18439–18447.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.2009316117

EISSN

1091-6490

Publication Date

August 4, 2020

Volume

117

Issue

31

Start / End Page

18439 / 18447

Location

United States

Related Subject Headings

  • Protein Processing, Post-Translational
  • Methylation
  • Lysine
  • Humans
  • Histones
  • Heterochromatin
  • DNA Methylation
  • DNA (Cytosine-5-)-Methyltransferase 1