{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:31:06Z","timestamp":1779251466614,"version":"3.51.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010757","name":"National Centre for the Replacement Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["NC\/M000834\/1"],"award-info":[{"award-number":["NC\/M000834\/1"]}],"id":[{"id":"10.13039\/501100010757","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010757","name":"National Centre for the Replacement Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["NCK500355\/1"],"award-info":[{"award-number":["NCK500355\/1"]}],"id":[{"id":"10.13039\/501100010757","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EPA Cephalosporin Fund","award":["CF331"],"award-info":[{"award-number":["CF331"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hydroxamate-based lysine deacetylase inhibitors (KDACis) are approved for clinical use against certain cancers. However, intrinsic and acquired resistance presents a major problem. Treatment of cells with hydroxamates such as trichostatin A (TSA) leads to rapid preferential acetylation of histone H3 already trimethylated on lysine 4 (H3K4me3), although the importance of this H3K4me3-directed acetylation in the biological consequences of KDACi treatment is not known. We address this utilizing Dictyostelium discoideum strains lacking H3K4me3 due to disruption of the gene encoding the Set1 methyltransferase or mutations in endogenous H3 genes. Loss of H3K4me3 confers resistance to TSA-induced developmental inhibition and delays accumulation of H3K9Ac and H3K14Ac. H3K4me3-directed H3Ac is mediated by Sgf29, a subunit of the SAGA acetyltransferase complex that interacts with H3K4me3 via a tandem tudor domain (TTD). We identify an Sgf29 orthologue in Dictyostelium with a TTD that specifically recognizes the H3K4me3 modification. Disruption of the gene encoding Sgf29 delays accumulation of H3K9Ac and abrogates H3K4me3-directed H3Ac. Either loss or overexpression of Sgf29 confers developmental resistance to TSA. Our results demonstrate that rapid acetylation of H3K4me3 histones regulates developmental sensitivity to TSA. Levels of H3K4me3 or Sgf29 will provide useful biomarkers for sensitivity to this class of chemotherapeutic drug.<\/jats:p>","DOI":"10.1093\/nar\/gkab154","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T15:10:40Z","timestamp":1614352240000},"page":"3781-3795","source":"Crossref","is-referenced-by-count":23,"title":["Methylation-directed acetylation of histone H3 regulates developmental sensitivity to histone deacetylase inhibition"],"prefix":"10.1093","volume":"49","author":[{"given":"Li-Yao","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duen-Wei","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1290-8326","authenticated-orcid":false,"given":"Catherine J","family":"Pears","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"2021041802165965900_B1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/ng1966","article-title":"Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome","volume":"39","author":"Heintzman","year":"2007","journal-title":"Nat. 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