PXD049993-1

PXD049993 is an original dataset announced via ProteomeXchange.

Title	Histone ubiquitination-methylation crosstalk involving UHRF1 and SUV39H1/2 reinforces heterochromatin states in response to DNA hypomethylation
Description	Histone H3 mono-ubiquitination, catalyzed by the RING E3 ubiquitin ligase UHRF1, is appreciated as a docking site for DNMT1 during DNA replication to facilitate DNA methylation maintenance. Its functions beyond this are unknown. Here, we identify simultaneous increases in UHRF1-dependent H3K18ub and SUV39H1/2-dependent H3K9me3 as prominent epigenetic alterations accompanying DNA hypomethylation induced by DNMT1 inhibition. Integrative epigenomics analyses reveal that transient accumulation of hemi-methylated DNA, resulting from incomplete DNA methylation maintenance, stimulates UHRF1-dependent H3K18ub at CpG islands that nucleates new domains of H3K9me3 and impedes PRC2 activity in these genomic regions. Notably, H3K18ub enhances the methyltransferase activity of SUV39H1/2, leading to increased H3K9me3 at these CpG island promoters. Blocking H3K18ub-dependent SUV39H1/2 activity enhances the efficacy of DNMT1 inhibitors. Collectively, these findings reveal a novel histone ubiquitination-methylation crosstalk mechanism that reinforces heterochromatin states in the absence of DNA methylation and proposes new strategies for improving cancer epigenetic therapy.
HostingRepository	PRIDE
AnnounceDate	2024-12-02
AnnouncementXML	Submission_2024-12-02_12:52:58.989.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simone Sidoli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-21 06:54:58	ID requested
⏵ 1	2024-12-02 12:52:59	announced

Dataset with its publication pending

submitter keyword: UHRF1, SUV39H1/2, epigenetic therapy, histone ubiquitination,DNA methylation, histone methylation

Simone Sidoli
contact affiliation	Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States
contact email	simone.sidoli@einsteinmed.edu
lab head
Simone Sidoli
contact affiliation	Albert Einstein College of Medicine
contact email	simone.sidoli@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049993
     1. Label: PRIDE project
     2. Name: Histone ubiquitination-methylation crosstalk involving UHRF1 and SUV39H1/2 reinforces heterochromatin states in response to DNA hypomethylation