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Still, the molecular function of ARID5B remains largely uncharacterized. Here, we employ a combination of proteomics, genomics, and transcriptomics to describe the molecular mechanisms of ARID5B. We identify that ARID5B interacts with MIER1, C16ORF87, HDAC1, and HDAC2 forming a chromatin repressor complex. By CUT&amp;RUN, we mapped ARID5B binding in active regions of the genome, tethering HDAC1 and HDAC2 to distal regulatory elements and promoters. Genes actively repressed by the ARID5B repressor complex are involved in B-cell proliferation and B-cell\u2013specific signaling. Together, we describe how ARID5B assembles into a repressor complex and regulates B-cell\u2013specific processes. Understanding its molecular mechanism will help elucidating how noncoding germline variants at ARID5B predispose to B-ALL.<\/jats:p>","DOI":"10.1093\/nar\/gkag628","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T11:53:20Z","timestamp":1781092400000},"source":"Crossref","is-referenced-by-count":0,"title":["Leukemia risk factor ARID5B coordinates HDAC-mediated transcriptional repression"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6360-873X","authenticated-orcid":false,"given":"Ana P","family":"Kutschat","sequence":"first","affiliation":[{"name":"St. Anna Children\u2019s Cancer Research Institute (CCRI) , 1090 Vienna ,","place":["Austria"]},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences , 1090 Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3666-8005","authenticated-orcid":false,"given":"Fabian","family":"Frommelt","sequence":"additional","affiliation":[{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences , 1090 Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianda L","family":"Santini","sequence":"additional","affiliation":[{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences , 1090 Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"St. Anna Children\u2019s Cancer Research Institute (CCRI) , 1090 Vienna ,","place":["Austria"]},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences , 1090 Vienna 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,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6149-3342","authenticated-orcid":false,"given":"Gerlinde","family":"Karbon","sequence":"additional","affiliation":[{"name":"St. Anna Children\u2019s Cancer Research Institute (CCRI) , 1090 Vienna ,","place":["Austria"]},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences , 1090 Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0570-1768","authenticated-orcid":false,"given":"Giulio","family":"Superti-Furga","sequence":"additional","affiliation":[{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences , 1090 Vienna ,","place":["Austria"]},{"name":"Center for Physiology and Pharmacology, Medical University of Vienna , 1090 Vienna 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