PXD067197-1

PXD067197 is an original dataset announced via ProteomeXchange.

Title	Molecular mechanism of co-transcriptional H3K36 methylation by SETD2
Description	H3K36me3 is a hallmark of actively and recently transcribed genes and contributes to cellular memory and identity. The deposition of H3K36me3 occurs co-transcriptionally when the methyltransferase SETD2 associates with RNA polymerase II. Using electron microscopy assisted by protein-protein crosslinking mass spectrometry, we solved three cryo-EM structures of SETD2 bound to Pol II elongation complexes at different states of nucleosome passage. Together with functional probing, our results suggest a 3-step mechanism of transcription-coupled H3K36me3 deposition. First, binding to the elongation factor SPT6 tethers the catalytic SET domain in proximity to the upstream DNA. Second, Pol II nucleosome passage leads to the transfer of a hexasome from downstream to upstream, poised for methylation. Finally, continued transcription leads to upstream nucleosome reassembly, partial dissociation of the histone chaperone FACT and sequential methylation of both H3 tails, completing H3K36me3 deposition of an upstream nucleosome after RNA polymerase II passage.
HostingRepository	PRIDE
AnnounceDate	2025-09-18
AnnouncementXML	Submission_2025-09-18_08:03:15.307.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Olexandr Dybkov
SpeciesList	scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-11 07:52:45	ID requested
⏵ 1	2025-09-18 08:03:15	announced

Dataset with its publication pending

submitter keyword: histone chaperone FACT, CXMS, SETD2,RNA polymerase II, transcription elongation

Henning Urlaub
contact affiliation	Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, Germany. Bioanalytics Group, Institute of Clinical Chemistry, University Medical Center Goettingen, Germany.
contact email	henning.urlaub@mpinat.mpg.de
lab head
Olexandr Dybkov
contact affiliation	Max Planck Institute for Multidisciplinary Sciences
contact email	odybkov@gwdg.de
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/2025/09/PXD067197

PRIDE project URI

• PRIDE
  1. PXD067197
     1. Label: PRIDE project
     2. Name: Molecular mechanism of co-transcriptional H3K36 methylation by SETD2