9E0G
A focus of tetramer (2) of the cryo-EM structure of human DNMT3A2-DNMT3B3 complex bound to di-nucleosome
Summary for 9E0G
| Entry DOI | 10.2210/pdb9e0g/pdb |
| Related | 9E00 9E05 |
| EMDB information | 47355 |
| Descriptor | Isoform 3 of DNA (cytosine-5)-methyltransferase 3B, DNA (cytosine-5)-methyltransferase 3A, ZINC ION, ... (4 entities in total) |
| Functional Keywords | dnmt3a2, dnmt3b3, dna methylation, di-nucleosome, dna binding protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 330591.69 |
| Authors | Xie, X.,Zhou, X.E.,Worden, E.J.,Jones, P.A. (deposition date: 2024-10-17, release date: 2026-02-18, Last modification date: 2026-08-12) |
| Primary citation | Xie, X.,Liu, M.,Chua, G.N.L.,Zhou, X.E.,Dykstra, M.L.,Liu, S.,Jones, P.A.,Worden, E.J. Nucleosome spacing regulates linker methylation by DNMT3A2/3B3. Mol.Cell, 86:834-850.e9, 2026 Cited by PubMed Abstract: De novo CpG methylation (mCpG) is deposited by DNMT3A and DNMT3B, which target DNA linkers between nucleosomes. Cells contain millions of unique linkers, but the rules dictating which linkers get targeted by DNMT3 enzymes are not understood. We show that nucleosome spacing controls linker DNA methylation and H3K36me2 recognition by human DNMT3A2/3B3, linking de novo methylation to chromatin architecture. We present structures of DNMT3A2/3B3 bound to dinucleosomes, revealing that short linkers promote dinucleosome bridging, blocking access to linker DNA and suppressing methylation, whereas long linkers allow DNMT3A2/3B3 to engage each nucleosome separately and methylate linker DNA. Finally, we show that DNMT3A2/3B3 positions proline-tryptophan-tryptophan-proline (PWWP) domains to scan for H3K36me2. However, H3K36me2 recognition is blocked when DNMT3A2/3B3 bridges dinucleosomes with short linkers, imposing an additional structural constraint on DNMT3A2/3B3 function. Together, these findings uncover the mechanisms that govern de novo methylation in chromatin and explain how DNMT3 enzymes target linkers in cells. PubMed: 41742418DOI: 10.1016/j.molcel.2026.01.030 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.72 Å) |
Structure validation
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