{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:21:12Z","timestamp":1768512072137,"version":"3.49.0"},"posted":{"date-parts":[[2024,5,30]]},"group-title":"Genetics","reference-count":61,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Azole resistance in the pathogenic yeast\n                  <jats:italic>Candida glabrata<\/jats:italic>\n                  is a serious clinical complication and increasing in frequency. The majority of resistant organisms have been found to contain a substitution mutation in the Zn2Cys6 zinc cluster-containing transcription factor Pdr1. These mutations typically lead to this factor driving high, constitutive expression of target genes like the ATP-binding cassette transporter-encoding gene\n                  <jats:italic>CDR1<\/jats:italic>\n                  . Overexpression of Cdr1 is required for the observed elevated fluconazole resistance exhibited by strains containing one of these hyperactive\n                  <jats:italic>PDR1<\/jats:italic>\n                  alleles. While the identity of hyperactive\n                  <jats:italic>PDR1<\/jats:italic>\n                  alleles has been extensively documented, the mechanisms underlying how these gain-of-function (GOF) forms of Pdr1 lead to elevated target gene transcription are not well understood. We have used a tandem affinity purification (TAP)-tagged form of Pdr1 to identify coactivator proteins that biochemically purify with the wild-type and two different GOF forms of Pdr1. Three coactivator proteins were found to associate with Pdr1: the SWI\/SNF complex Snf2 chromatin remodeling protein and two different components of the SAGA complex, Spt7 and Ngg1. We found that deletion mutants lacking either\n                  <jats:italic>SNF2<\/jats:italic>\n                  or\n                  <jats:italic>SPT7<\/jats:italic>\n                  exhibited growth defects, even in the absence of fluconazole challenge. To overcome these issues, we employed a conditional degradation system to acutely deplete these coactivators and determined that loss of either coactivator complex, SWI\/SNF or SAGA, caused defects in Pdr1-dependent transcription. A double degron strain that could be depleted for both SWI\/SNF and SAGA exhibited a profound defect in\n                  <jats:italic>PDR1<\/jats:italic>\n                  autoregulation, revealing that these complexes work together to ensure high level Pdr1-dependent gene transcription.\n                <\/jats:p>","DOI":"10.1101\/2024.05.24.595833","type":"posted-content","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T11:20:42Z","timestamp":1717068042000},"source":"Crossref","is-referenced-by-count":0,"title":["Overlapping coactivator function is required for transcriptional activation by the\n                  <i>Candida glabrata<\/i>\n                  Pdr1 transcription factor"],"prefix":"10.64898","author":[{"given":"Thomas P.","family":"Conway","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Simonicova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7163-1120","authenticated-orcid":false,"given":"W. 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