PXD024604 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Chd1 regulates repair of promoter-proximal DNA breaks to sustain hypertranscription in embryonic stem cells |
Description | Stem and progenitor cells undergo a global elevation of nascent transcription, or hypertranscription, during key developmental transitions involving rapid cell proliferation. The chromatin remodeler Chd1 binds to RNA Pol I and II genes and is required for hypertranscription in embryonic stem (ES) cells in vitro and the early post-implantation epiblast in vivo. Biochemically, Chd1 has been shown to facilitate transcription at least in part by removing nucleosomal barriers to elongation, but its mechanism of action in stem cells remains poorly understood. Here we report a novel role for Chd1 in the repair of promoter-proximal endogenous double-stranded DNA breaks (DSBs) in ES cells. An unbiased proteomics approach revealed that Chd1 interacts with several DNA repair factors including ATM, Parp1, Kap1 and Topoisomerase 2. We show that wild-type ES cells display high levels of phosphorylated H2AX and Kap1 at chromatin, notably at rDNA in the nucleolus, in a Chd1-dependent manner. Loss of Chd1 leads to an extensive accumulation of DSBs at Chd1 target Pol II genes and rDNA. Genes prone to DNA breaks in Chd1-null ES cells tend to be longer genes with GC-rich promoters, a more labile nucleosomal structure and roles in chromatin organization, transcription and signaling. These results reveal a vulnerability of hypertranscribing stem cells to endogenous DNA breaks, with important implications for developmental and cancer biology. |
HostingRepository | PRIDE |
AnnounceDate | 2021-06-15 |
AnnouncementXML | Submission_2021-06-14_22:32:44.262.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Andrew Williamson |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-03-09 01:29:56 | ID requested | |
⏵ 1 | 2021-06-14 22:32:44 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Mouse Stem cell Orbitrap immunoprecipitation mass spectrometry |
Contact List
Miguel Ramalho-Santos |
contact affiliation | Lunenfeld-Tanenbaum Research Institute and Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1X5, Canada |
contact email | mrsantos@lunenfeld.ca |
lab head | |
Andrew Williamson |
contact affiliation | Thermo Fisher Scientific |
contact email | andrew.williamson@thermofisher.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
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[ - ]
- PRIDE
- PXD024604
- Label: PRIDE project
- Name: Chd1 regulates repair of promoter-proximal DNA breaks to sustain hypertranscription in embryonic stem cells