PXD056554-1

PXD056554 is an original dataset announced via ProteomeXchange.

Title	The N-terminal region of DNMT3A combines multiple chromatin reading motifs to guide recruitment
Description	DNA 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-16
AnnouncementXML	Submission_2024-10-16_07:59:45.065.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christos Spanos
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	2024-10-07 09:38:13	ID requested
⏵ 1	2024-10-16 07:59:45	announced

10.1101/2023.10.29.564595;

submitter keyword: DNMT3A, UDR, histone modifications, nucleosomes, chromatin

Marcus Wislon
contact affiliation	The University of Edinburgh
contact email	marcus.wilson@ed.ac.uk
lab head
Christos Spanos
contact affiliation	University of Edinburgh
contact email	spanos.christos@gmail.com
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/2024/10/PXD056554

PRIDE project URI

• PRIDE
  1. PXD056554
     1. Label: PRIDE project
     2. Name: The N-terminal region of DNMT3A combines multiple chromatin reading motifs to guide recruitment