7LMM

Crystal structure of bovine DNMT1 BAH1 domain in complex with H4K20me2

Summary for 7LMM

• Entry DOI: 10.2210/pdb7lmm/pdb
• Related: 7LMK
• Descriptor: DNA (cytosine-5)-methyltransferase 1,DNA (cytosine-5)-methyltransferase 1, Histone H4, ZINC ION, ... (4 entities in total)
• Functional Keywords: dna methylation, dna methyltransferase 1, histone modification, allosteric regulation, transferase
• Biological source: Bos taurus (Bovine); More
• Total number of polymer chains: 8
• Total formula weight: 77932.81

Authors

Ren, W.,Song, J. (deposition date: 2021-02-05, release date: 2021-02-17, Last modification date: 2023-10-18)

Primary citation

Ren, W.,Fan, H.,Grimm, S.A.,Kim, J.J.,Li, L.,Guo, Y.,Petell, C.J.,Tan, X.F.,Zhang, Z.M.,Coan, J.P.,Yin, J.,Kim, D.I.,Gao, L.,Cai, L.,Khudaverdyan, N.,Cetin, B.,Patel, D.J.,Wang, Y.,Cui, Q.,Strahl, B.D.,Gozani, O.,Miller, K.M.,O'Leary, S.E.,Wade, P.A.,Wang, G.G.,Song, J.
DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation.
Nat Commun, 12:2490-2490, 2021

PubMed Abstract: 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 (DNMT1). Engagement of DNMT1-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.

PubMed: 33941775
DOI: 10.1038/s41467-021-22665-4

Experimental method

X-RAY DIFFRACTION (2.798 Å)