PXD043031

PXD043031 is an original dataset announced via ProteomeXchange.

Title	Inhibition of DNMT1 methyltransferase activity via glucose-regulated O-GlcNAcylation alters the epigenome
Description	The DNA methyltransferase activity of DNMT1 is vital for genomic maintenance of DNA methylation. We report here that DNMT1 function is regulated by O-GlcNAcylation, a protein modification that is sensitive to glucose levels, and that elevated O-GlcNAcylation of DNMT1 from high glucose environment leads to alterations to the epigenome. Using mass spectrometry and complementary alanine mutation experiments, we identified S878 as the major residue that is O-GlcNAcylated on DNMT1. Functional studies further revealed that O-GlcNAcylation of DNMT1-S878 results in an inhibition of methyltransferase activity, resulting in a general loss of DNA methylation that is preferentially at partially methylated domains (PMDs). This loss of methylation corresponds with an increase in DNA damage and apoptosis. These results establish O-GlcNAcylation of DNMT1 as a mechanism through which the epigenome is regulated by glucose metabolism and implicates a role for glycosylation of DNMT1 in metabolic diseases characterized by hyperglycemia.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:04:22.214.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD043031
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Heon Shin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylation to amine thiol - site S; Hex1HexNAc1NeuAc1 O-glycosylated serine; phosphorylation to amine thiol - site T; Hex1HexNAc1NeuAc1 O-glycosylated threonine; monohydroxylated residue; Hex-HexNAc; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-15 13:22:08	ID requested
1	2023-07-26 11:50:28	announced
⏵ 2	2023-11-14 09:04:28	announced	2023-11-14: Updated project metadata.

10.6019/PXD043031;

Shin H, Leung A, Costello KR, Senapati P, Kato H, Moore RE, Lee M, Lin D, Tang X, Pirrotte P, Bouman Chen Z, Schones DE, -GlcNAcylation alters the epigenome. Elife, 12():(2023) [pubmed]

submitter keyword: Metabolism, O-GlcNAcylation,Epigenetics, Hyperglycemia

Dustin E Schones
contact affiliation	Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, CA 91010
contact email	dschones@coh.org
lab head
Heon Shin
contact affiliation	City of Hope
contact email	hshin@coh.org
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/07/PXD043031

PRIDE project URI

• PRIDE
  1. PXD043031
     1. Label: PRIDE project
     2. Name: Inhibition of DNMT1 methyltransferase activity via glucose-regulated O-GlcNAcylation alters the epigenome