{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T02:39:06Z","timestamp":1787625546801,"version":"build-2736575974"},"reference-count":58,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["5R21AI113390"],"award-info":[{"award-number":["5R21AI113390"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Long-term azole treatment of patients with chronic\n                    <jats:named-content content-type=\"genus-species\">Candida albicans<\/jats:named-content>\n                    infections can lead to drug resistance. Gain-of-function (GOF) mutations in the transcription factor Mrr1 and the consequent transcriptional activation of\n                    <jats:italic>MDR1<\/jats:italic>\n                    , a drug efflux coding gene, is a common pathway by which this human fungal pathogen acquires fluconazole resistance. This work elucidates the previously unknown downstream transcription mechanisms utilized by hyperactive Mrr1. We identified the Swi\/Snf chromatin remodeling complex as a key coactivator for Mrr1, which is required to maintain basal and induced open chromatin, and Mrr1 occupancy, at the\n                    <jats:italic>MDR1<\/jats:italic>\n                    promoter. Deletion of\n                    <jats:italic>snf2<\/jats:italic>\n                    , the catalytic subunit of Swi\/Snf, largely abrogates the increases in\n                    <jats:italic>MDR1<\/jats:italic>\n                    expression and fluconazole MIC observed in\n                    <jats:italic>MRR1<\/jats:italic>\n                    <jats:sup>GOF<\/jats:sup>\n                    mutant strains. Mediator positively and negatively regulates key Mrr1 target promoters. Deletion of the Mediator tail module\n                    <jats:italic>med3<\/jats:italic>\n                    subunit reduces, but does not eliminate, the increased\n                    <jats:italic>MDR1<\/jats:italic>\n                    expression and fluconazole MIC conferred by\n                    <jats:italic>MRR1<\/jats:italic>\n                    <jats:sup>GOF<\/jats:sup>\n                    mutations. Eliminating the kinase activity of the Mediator Ssn3 subunit suppresses the decreased\n                    <jats:italic>MDR1<\/jats:italic>\n                    expression and fluconazole MIC of the\n                    <jats:italic>snf2<\/jats:italic>\n                    null mutation in\n                    <jats:italic>MRR1<\/jats:italic>\n                    <jats:sup>GOF<\/jats:sup>\n                    strains. Ssn3 deletion also suppresses\n                    <jats:italic>MDR1<\/jats:italic>\n                    promoter histone displacement defects in\n                    <jats:italic>snf2<\/jats:italic>\n                    null mutants. The combination of this work with studies on other hyperactive zinc cluster transcription factors that confer azole resistance in fungal pathogens reveals a complex picture where the induction of drug efflux pump expression requires the coordination of multiple coactivators. The observed variations in transcription factor and target promoter dependence of this process may make the search for azole sensitivity-restoring small molecules more complicated.\n                  <\/jats:p>","DOI":"10.1128\/aac.01344-17","type":"journal-article","created":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T20:40:16Z","timestamp":1502743216000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":47,"title":["Candida albicans Swi\/Snf and Mediator Complexes Differentially Regulate Mrr1-Induced\n                    <i>MDR1<\/i>\n                    Expression and Fluconazole Resistance"],"prefix":"10.1128","volume":"61","author":[{"given":"Zhongle","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence 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