Scholars@Duke

DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation.

Publication ,  Journal Article
Ren, W; Fan, H; Grimm, SA; Kim, JJ; Li, L; Guo, Y; Petell, CJ; Tan, X-F; Zhang, Z-M; Coan, JP; Yin, J; Kim, DI; Gao, L; Cai, L; Çetin, B ...
Published in: Nat Commun
May 3, 2021
Published version (DOI) Link to item

DNA methylation and trimethylated histone H4 Lysine 20 (H4K20me3) constitute two important heterochromatin-enriched marks that frequently cooperate in silencing repetitive elements of the mammalian genome. However, it remains elusive how these two chromatin modifications crosstalk. Here, we report that DNA methyltransferase 1 (DNMT1) specifically 'recognizes' H4K20me3 via its first bromo-adjacent-homology domain (DNMT1BAH1). Engagement of DNMT1BAH1-H4K20me3 ensures heterochromatin targeting of DNMT1 and DNA methylation at LINE-1 retrotransposons, and cooperates with the previously reported readout of histone H3 tail modifications (i.e., H3K9me3 and H3 ubiquitylation) by the RFTS domain to allosterically regulate DNMT1's activity. Interplay between RFTS and BAH1 domains of DNMT1 profoundly impacts DNA methylation at both global and focal levels and genomic resistance to radiation-induced damage. Together, our study establishes a direct link between H4K20me3 and DNA methylation, providing a mechanism in which multivalent recognition of repressive histone modifications by DNMT1 ensures appropriate DNA methylation patterning and genomic stability.

Duke Scholars

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

Published In

Nat Commun

DOI

10.1038/s41467-021-22665-4

EISSN

2041-1723

Publication Date

May 3, 2021

Volume

12

Issue

1

Start / End Page

2490

Location

England

Related Subject Headings

  • Mice
  • Long Interspersed Nucleotide Elements
  • Histones
  • Heterochromatin
  • Genomic Instability
  • Genome
  • DNA Methylation
  • DNA (Cytosine-5-)-Methyltransferase 1
  • Crystallography, X-Ray
  • Cell Line
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ren, W., Fan, H., Grimm, S. A., Kim, J. J., Li, L., Guo, Y., … Song, J. (2021). DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation. Nat Commun, 12(1), 2490. https://doi.org/10.1038/s41467-021-22665-4
Ren, Wendan, Huitao Fan, Sara A. Grimm, Jae Jin Kim, Linhui Li, Yiran Guo, Christopher James Petell, et al. “DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation.” Nat Commun 12, no. 1 (May 3, 2021): 2490. https://doi.org/10.1038/s41467-021-22665-4.
Ren W, Fan H, Grimm SA, Kim JJ, Li L, Guo Y, et al. DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation. Nat Commun. 2021 May 3;12(1):2490.
Ren, Wendan, et al. “DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation.” Nat Commun, vol. 12, no. 1, May 2021, p. 2490. Pubmed, doi:10.1038/s41467-021-22665-4.
Ren W, Fan H, Grimm SA, Kim JJ, Li L, Guo Y, Petell CJ, Tan X-F, Zhang Z-M, Coan JP, Yin J, Kim DI, Gao L, Cai L, Khudaverdyan N, Çetin B, Patel DJ, Wang Y, Cui Q, Strahl BD, Gozani O, Miller KM, O’Leary SE, Wade PA, Wang GG, Song J. DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation. Nat Commun. 2021 May 3;12(1):2490.

Published In

Nat Commun

DOI

10.1038/s41467-021-22665-4

EISSN

2041-1723

Publication Date

May 3, 2021

Volume

12

Issue

1

Start / End Page

2490

Location

England

Related Subject Headings

  • Mice
  • Long Interspersed Nucleotide Elements
  • Histones
  • Heterochromatin
  • Genomic Instability
  • Genome
  • DNA Methylation
  • DNA (Cytosine-5-)-Methyltransferase 1
  • Crystallography, X-Ray
  • Cell Line