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Series GSE152639 Query DataSets for GSE152639
Status Public on Jun 17, 2020
Title Structure of DNA methyltransferases DNMT3A/DNMT3B bound to a nucleosome [seq]
Organism synthetic construct
Experiment type Methylation profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary CpG methylation by the 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 favor the methylation of linker DNA at positioned nucleosomes3,4. Here we present the cryo-EM 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 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.
 
Overall design We verified the catalytic activity of wildtype and mutant DNMT3A2/3B3 complex using bisulfite sequencing. We also used limited micrococcal nuclease (MNase) digestion followed by sequencing to map the binding of DNMT3A2/3B3 complex to in vitro assembled nucleosome.
 
Contributor(s) Liu M, Xu T, Zhou EX, Liang G, Zhao G, Xu EH, Melcher K, Jones PA
Citation(s) 32968275
Submission date Jun 16, 2020
Last update date Oct 07, 2020
Contact name Peter A Jones
E-mail(s) Peter.Jones@vai.org
Organization name Van Andel Research Institute
Department Center for Epigenetics
Lab Jones Lab
Street address 333 Bostwick Ave
City Grand Rapids
State/province MI
ZIP/Postal code 49503
Country USA
 
Platforms (1)
GPL17769 Illumina MiSeq (synthetic construct)
Samples (20)
GSM4622607 T10_WT
GSM4622608 T1_R740E
GSM4622609 T2_R743E
This SubSeries is part of SuperSeries:
GSE152640 Structure of DNA methyltransferases DNMT3A/DNMT3B bound to a nucleosome
Relations
BioProject PRJNA639948
SRA SRP267769

Download family Format
SOFT formatted family file(s) SOFTHelp
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Supplementary file Size Download File type/resource
GSE152639_NCP301.fa.gz 194 b (ftp)(http) FA
GSE152639_RAW.tar 140.0 Kb (http)(custom) TAR (of BW, VCF)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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