{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T15:58:59Z","timestamp":1781193539531,"version":"3.54.1"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Dutch Cancer Foundation","award":["KWF 12725"],"award-info":[{"award-number":["KWF 12725"]}]},{"name":"Dutch Cancer Foundation","award":["KWF 15286"],"award-info":[{"award-number":["KWF 15286"]}]},{"name":"Dutch Cancer Foundation","award":["KWF 11013"],"award-info":[{"award-number":["KWF 11013"]}]},{"DOI":"10.13039\/501100004622","name":"Dutch Cancer Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Loss-of-function mutations in BCOR, a 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. Paradoxically, leukemic stem cell viability in BCOR wild-type AMLs strongly depends on PRC1.1 activity. Here, we use BCOR and KDM2B degron models to study PRC1.1 dependency in leukemic cells and find that BCOR is a bridging factor tethering the catalytic and chromatin-binding moieties of the PRC1.1 complex. BCOR degradation induces a quick localized loss of H2AK119ub at PRC1.1 target genes, whereas PRC2-induced H3K27me3 remains unaffected. Degron-mediated depletion of BCOR or KDM2B induces a rapid but time-dependent transcriptional induction, whereby late-upregulated genes are more heavily decorated with H3K27me3 compared to early-upregulated genes. Combined PRC1.1 inactivation and PRC2 inhibition further amplifies gene induction, suggesting collaborative yet distinct control over target genes. Strikingly, both JARID2\/AEBP2 and SUZ12 knockout cells, devoid of PRC2.2 or PRC2.1\/PRC2.2 respectively, retain PRC1.1 loss-induced transcriptional activation, underscoring that PRC1.1 can repress target genes independently 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.<\/jats:p>","DOI":"10.1093\/nar\/gkag529","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T12:08:55Z","timestamp":1778760535000},"source":"Crossref","is-referenced-by-count":0,"title":["Sustained PRC1.1 activity preserves gene repression independently of PRC2.2 and restrains leukemic cell differentiation"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0742-4335","authenticated-orcid":false,"given":"Fatemeh","family":"Mojallali","sequence":"first","affiliation":[{"name":"Department of Experimental Hematology, University Medical Center Groningen, University of Groningen , Hanzeplein 1, 9713 GZGroningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5899-9528","authenticated-orcid":false,"given":"Alessandra","family":"De\u00a0Meis","sequence":"additional","affiliation":[{"name":"Department of Experimental Hematology, University Medical Center Groningen, University of Groningen , Hanzeplein 1, 9713 GZGroningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2463-5196","authenticated-orcid":false,"given":"Sinne G","family":"Alkema","sequence":"additional","affiliation":[{"name":"Department of Experimental Hematology, University Medical Center Groningen, University of Groningen , Hanzeplein 1, 9713 GZGroningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjerk Jan","family":"Atsma","sequence":"additional","affiliation":[{"name":"Department of Experimental Hematology, University Medical Center Groningen, University of Groningen , Hanzeplein 1, 9713 GZGroningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanna M","family":"Hogeling","sequence":"additional","affiliation":[{"name":"Department of Experimental Hematology, University Medical Center Groningen, University of Groningen , Hanzeplein 1, 9713 GZGroningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rianne","family":"Kloosterman","sequence":"additional","affiliation":[{"name":"Department of Experimental Hematology, University Medical Center Groningen, University of Groningen , Hanzeplein 1, 9713 GZGroningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eve","family":"Ioannou","sequence":"additional","affiliation":[{"name":"Department of Experimental Hematology, University Medical Center Groningen, University of Groningen , Hanzeplein 1, 9713 GZGroningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albertus T J","family":"Wierenga","sequence":"additional","affiliation":[{"name":"Department of Experimental Hematology, University Medical Center Groningen, University of Groningen , Hanzeplein 1, 9713 GZGroningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerwin","family":"Huls","sequence":"additional","affiliation":[{"name":"Department of Experimental Hematology, University Medical Center Groningen, University of Groningen , Hanzeplein 1, 9713 GZGroningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost H A","family":"Martens","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Science and Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen , Geert Grooteplein 28, 6525 GA Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Jacob","family":"Schuringa","sequence":"additional","affiliation":[{"name":"Department of Experimental Hematology, University Medical Center Groningen, University of Groningen , Hanzeplein 1, 9713 GZGroningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1992-9608","authenticated-orcid":false,"given":"Vincent","family":"van\u00a0den\u00a0Boom","sequence":"additional","affiliation":[{"name":"Department of Experimental Hematology, University Medical Center Groningen, University of Groningen , Hanzeplein 1, 9713 GZGroningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"2026061111101256200_B1","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1038\/s41580-021-00398-y","article-title":"The molecular 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