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Resistance to PARPi is a growing clinical problem in the treatment of high grade serous ovarian carcinoma (HGSOC). Acetylation of histone H3 lysine 14 (H3K14ac) and associated histone acetyltransferases (HATs) and epigenetic readers have known functions in DNA repair and replication. Our objectives are to examine their expression and activities in the context of PARPi\u2010resistant HGSOC, and to determine if targeting H3K14ac or associated proteins has therapeutic potential. Using mass spectrometry profiling of histone modifications, we observed increased H3K14ac enrichment in PARPi\u2010resistant HGSOC cells relative to isogenic PARPi\u2010sensitive lines. By reverse\u2010transcriptase quantitative PCR\u00a0and RNA\u2010seq, we also observed altered expression of numerous HATs in PARPi\u2010resistant HGSOC cells and a PARPi\u2010resistant PDX model. Knockdown of HATs only modestly altered PARPi response, although knockdown and inhibition of PCAF significantly increased resistance. Pharmacologic inhibition of HBO1 depleted H3K14ac but did not affect PARPi response. However, knockdown and inhibition of BRPF3, a bromodomain and PHD\u2010finger containing protein that is known to interact in a complex with HBO1, did reduce PARPi resistance. This study demonstrates that depletion of H3K14ac does not affect PARPi response in HGSOC. Our data suggest that the bromodomain function of HAT proteins, such as PCAF, or accessory proteins, such as BRPF3, may play a more direct role compared to direct HATs\u00a0function in PARPi response.<\/jats:p>","DOI":"10.1002\/mc.23610","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T06:35:10Z","timestamp":1690353310000},"page":"1717-1730","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Targeting BRPF3 moderately reverses olaparib resistance in high grade serous ovarian carcinoma"],"prefix":"10.1002","volume":"62","author":[{"given":"Benjamin G.","family":"Bitler","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Reproductive Sciences University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney 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