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PXD024604

PXD024604 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleChd1 regulates repair of promoter-proximal DNA breaks to sustain hypertranscription in embryonic stem cells
DescriptionStem 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.
HostingRepositoryPRIDE
AnnounceDate2021-06-15
AnnouncementXMLSubmission_2021-06-14_22:32:44.262.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAndrew Williamson
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-03-09 01:29:56ID requested
12021-06-14 22:32:44announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Mouse Stem cell Orbitrap immunoprecipitation mass spectrometry
Contact List
Miguel Ramalho-Santos
contact affiliationLunenfeld-Tanenbaum Research Institute and Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1X5, Canada
contact emailmrsantos@lunenfeld.ca
lab head
Andrew Williamson
contact affiliationThermo Fisher Scientific
contact emailandrew.williamson@thermofisher.com
dataset submitter
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Dataset FTP location
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