EMD-20281
The cryo-EM structure of the human DNMT3A2-DNMT3B3 complex bound to nucleosome.
EMD-20281
Single-particle2.94 Å
Deposition: 11/06/2019Map released: 17/06/2020
Last modified: 20/03/2024
Sample Organism:
Xenopus laevis,
synthetic construct,
Homo sapiens
Sample: A ternary complex of DNMT3A/B asymmetrically binds to the nucleosomes
Fitted models: 6pa7 (Avg. Q-score: 0.403)
Raw data: EMPIAR-11732
Deposition Authors: Xu TH
,
Liu M
Sample: A ternary complex of DNMT3A/B asymmetrically binds to the nucleosomes
Fitted models: 6pa7 (Avg. Q-score: 0.403)
Raw data: EMPIAR-11732
Deposition Authors: Xu TH
,
Liu M
Structure of nucleosome-bound DNA methyltransferases DNMT3A and DNMT3B.
Xu TH ,
Liu M,
Zhou XE,
Liang G ,
Zhao G ,
Xu HE ,
Melcher K ,
Jones PA
(2020) Nature , 586 , 151 - 155
,
Liu M,
Zhou XE,
Liang G ,
Zhao G ,
Xu HE ,
Melcher K ,
Jones PA
(2020) Nature , 586 , 151 - 155
Abstract:
CpG methylation by de novo DNA methyltransferases (DNMTs) 3A and 3B is essential for mammalian development and differentiation and is frequently dysregulated in cancer1. These two DNMTs preferentially bind to nucleosomes, yet cannot methylate the DNA wrapped around the nucleosome core2, and they favour the methylation of linker DNA at positioned nucleosomes3,4. Here we present the cryo-electron microscopy structure of a ternary complex of catalytically competent DNMT3A2, the catalytically inactive accessory subunit DNMT3B3 and a nucleosome core particle flanked by linker DNA. The catalytic-like domain of the accessory DNMT3B3 binds to the acidic patch of the nucleosome core, which orients the binding of DNMT3A2 to the linker DNA. The steric constraints of this arrangement suggest that nucleosomal DNA must be moved relative to the nucleosome core for de novo methylation to occur.
CpG methylation by de novo DNA methyltransferases (DNMTs) 3A and 3B is essential for mammalian development and differentiation and is frequently dysregulated in cancer1. These two DNMTs preferentially bind to nucleosomes, yet cannot methylate the DNA wrapped around the nucleosome core2, and they favour the methylation of linker DNA at positioned nucleosomes3,4. Here we present the cryo-electron microscopy structure of a ternary complex of catalytically competent DNMT3A2, the catalytically inactive accessory subunit DNMT3B3 and a nucleosome core particle flanked by linker DNA. The catalytic-like domain of the accessory DNMT3B3 binds to the acidic patch of the nucleosome core, which orients the binding of DNMT3A2 to the linker DNA. The steric constraints of this arrangement suggest that nucleosomal DNA must be moved relative to the nucleosome core for de novo methylation to occur.