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PXD056554

PXD056554 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe N-terminal region of DNMT3A combines multiple chromatin reading motifs to guide recruitment
DescriptionDNA methyltransferase 3A (DNMT3A) plays a critical role in establishing and maintaining DNA methylation patterns. However, the mechanisms underlying DNMT3A recruitment to and function within different chromatin environments remain unclear. Using a combination of biochemical and structural approaches we find that DNMT3A interacts using multiple interfaces with chromatin; directly binding generic nucleosome features as well as site-specific post-translational histone modifications. The N-terminal region, unique to the DNMT3A1 isoform, is essential for these interactions and stabilises H3K36me2-nucleosome recruitment. Intriguingly, in the same region critical for nucleosome binding we also map a ubiquitylation-dependent recruitment motif (UDR). The UDR binds specifically to ubiquitylated H2AK119, explaining the previously observed recruitment to Polycomb-occupied heterochromatin. A cryo-EM structure of DNMT3A1-DNMT3L with a modified nucleosome reveals that the UDR interacts with the nucleosome surface including the acidic patch. Previously unexplained disease-associated mutations are present in the UDR and ablate nucleosome interactions. This leads to an increased understanding of how DNMT3A1 recruitment occurs in the genome and highlights the importance of multivalent binding of DNMT3A to histone modifications and the nucleosome.
HostingRepositoryPRIDE
AnnounceDate2024-10-16
AnnouncementXMLSubmission_2024-10-16_07:59:45.065.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChristos Spanos
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-10-07 09:38:13ID requested
12024-10-16 07:59:45announced
Publication List
10.1101/2023.10.29.564595;
Keyword List
submitter keyword: DNMT3A, UDR, histone modifications, nucleosomes, chromatin
Contact List
Marcus Wislon
contact affiliationThe University of Edinburgh
contact emailmarcus.wilson@ed.ac.uk
lab head
Christos Spanos
contact affiliationUniversity of Edinburgh
contact emailspanos.christos@gmail.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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