Summary information and primary citation
- PDB-id
-
9e00;
DSSR-derived features in text and
JSON formats
- Class
- DNA binding protein
- Method
- cryo-EM (3.75 Å)
- Summary
- cryo-EM structure of human dnmt3a2-dnmt3b3 complex
bound to di-nucleosome
- Reference
-
Xie X, Liu M, Chua GNL, Zhou XE, Dykstra ML, Liu S, Jones
PA, Worden EJ (2026): "Nucleosome
spacing regulates linker methylation by DNMT3A2/3B3."
Mol.Cell, 86, 834-850.e9. doi:
10.1016/j.molcel.2026.01.030.
- 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.
