PXD045915-1
PXD045915 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Systematic perturbations of SETD2, NSD1, NSD2, NSD3 and ASH1L reveals their distinct contributions to H3K36 methylation |
| Description | Methylation of histone 3 lysine 36 (H3K36me) has emerged as an essential epigenetic component for the faithful regulation of gene expression. Despite its demonstrated importance in development, disease, and cancer, the molecular agents responsible for the deposition of H3K36me are not yet well understood. Here, we use a mouse mesenchymal stem cell model to comprehensively perturb the components of the H3K36me deposition machinery and infer the activities of the five most prominent players: SETD2, NSD1, NSD2, NSD3, and ASH1L. We find that H3K36me2 is the most abundant of the three methylation states and that it is predominantly deposited at intergenic regions by NSD1, and in part by NSD2. In contrast, H3K36me1/3 are most abundant within exons and have a positive correlation with gene expression. We further demonstrate that while SETD2 is responsible for depositing most H3K36me3, it also deposits a modest amount of H3K36me2 within transcribed genes. Additionally, loss of SETD2 results in an increase of exonic H3K36me1, suggesting that other H3K36 methyltransferases may prime gene bodies with lower methylation states ahead of transcription. Through a reductive approach, we uncover the genome-wide distribution patterns of NSD3- and ASH1L-catalyzed H3K36me2. While NSD1/2 establish broad intergenic H3K36me2 domains, NSD3 deposits broad H3K36me2 peaks centered on active promoter and enhancer regions. Meanwhile, the activity of ASH1L is focused primarily on the promoters of developmentally relevant genes, and our analyses implicate PBX2 as a potential recruitment factor for ASH1L to these regions. Overall, our study provides new insights into the regulation of H3K36me by the H3K36 methyltransferase family and helps to consolidate the wealth of previous observations in the context of a structured analysis. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-09-25 |
| AnnouncementXML | Submission_2024-09-25_11:18:58.092.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Jacek Majewski |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | Trimethyl; Dimethyl; Methyl; Acetyl |
| Instrument | Orbitrap Exploris 240 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2023-10-05 09:31:42 | ID requested | |
| ⏵ 1 | 2024-09-25 11:18:58 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: H3K36me, Epigenetic, methylation |
Contact List
| Jacek Majewski | |
|---|---|
| contact affiliation | Department of Human Genetics, McGill University |
| contact email | jacek.majewski@mcgill.ca |
| lab head | |
| Jacek Majewski | |
| contact affiliation | McGill University |
| contact email | jacek.majewski@mcgill.ca |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive.ucsd.edu/v06/MSV000093049/ |
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