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PXD065157-1

PXD065157 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSustained PRC1.1 activity preserves gene repression independent of PRC2.2 and suppresses leukemic cell differentiation
DescriptionLoss-of-function mutations in BCOR, subunit of the non-canonical Polycomb Repressive Complex 1.1 (PRC1.1), are frequently observed in acute myeloid leukemia (AML) and associate with adverse risk, but underlying mechanisms driving leukemogenesis remain elusive. Here, we find that BCOR is a bridging factor tethering the catalytic and chromatin-binding moieties of the PRC1.1 complex. Degron-mediated depletion of BCOR or KDM2B induces a rapid but time-dependent transcriptional induction, whereby early-upregulated genes have a distinct epigenetic profile compared to late-upregulated genes that are more heavily decorated with H3K27me3. Combined KDM2B degradation and PRC2 inhibition further amplifies gene induction suggesting distinct yet collaborative control over target genes. Strikingly, both JARID2/AEBP2 and SUZ12 knockout cells, completely devoid of PRC2 functionality, retain PRC1.1-loss induced transcriptional activation, underscoring that PRC1.1 can repress target genes independent of a downstream PRC2.2-canonical PRC1 repressive axis. Finally, combined targeting of PRC1.1 and PRC2 induces differentiation of leukemic cells emphasizing that co-targeting PRC1.1 and PRC2 represents a promising strategy to improve treatment of AML patients
HostingRepositoryPRIDE
AnnounceDate2026-06-15
AnnouncementXMLSubmission_2026-06-14_16:18:37.756.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJustina Clarinda Wolters
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-06-18 05:21:46ID requested
12026-06-14 16:18:38announced
Publication List
Mojallali F, De Meis A, Alkema SG, Atsma TJ, Hogeling SM, Kloosterman R, Ioannou E, Wierenga ATJ, Huls G, Martens JHA, Schuringa JJ, van den Boom V, Sustained PRC1.1 activity preserves gene repression independently of PRC2.2 and restrains leukemic cell differentiation. Nucleic Acids Res, 54(11):(2026) [pubmed]
10.1093/nar/gkag529;
Keyword List
submitter keyword: Human, Exploris480
Contact List
Dr. Justina Clarinda Wolters
contact affiliationDepartment of Pediatrics, UMCG, Groningen, The Netherlands
contact emailj.c.wolters@umcg.nl
lab head
Justina Clarinda Wolters
contact affiliationUMCG
contact emailj.c.wolters@umcg.nl
dataset submitter
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Dataset FTP location
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