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In this study, we determined that cells lacking Set1 or Set1 complex members that disrupt H3K4 methylation have a growth defect when grown in the presence of the antifungal drug Brefeldin A (BFA), indicating that H3K4 methylation is needed for BFA resistance. To determine the role of Set1 in BFA resistance, we discovered that Set1 is important for the expression of genes in the ergosterol biosynthetic pathway, including the rate-limiting enzyme HMG-CoA reductase. Consequently, deletion of\n                    <jats:italic>SET1<\/jats:italic>\n                    leads to a reduction in HMG-CoA reductase protein and total cellular ergosterol. In addition, the lack of Set1 results in an increase in the expression of\n                    <jats:italic>DAN1<\/jats:italic>\n                    and\n                    <jats:italic>PDR11<\/jats:italic>\n                    , two genes involved in ergosterol uptake. The increase in expression of uptake genes in\n                    <jats:italic>set1\u0394<\/jats:italic>\n                    cells allows sterols such as cholesterol and ergosterol to be actively taken up under aerobic conditions. Interestingly, when grown in the presence of ergosterol\n                    <jats:italic>set1\u0394<\/jats:italic>\n                    cells become resistant to BFA, indicating that proper ergosterol levels are needed for antifungal drug resistance. These data show that H3K4 methylation impacts gene expression and output of a biologically and medically relevant pathway and determines why cells lacking H3K4 methylation have antifungal drug sensitivity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1215768110","type":"journal-article","created":{"date-parts":[[2013,2,4]],"date-time":"2013-02-04T23:29:25Z","timestamp":1360020565000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":37,"title":["H3K4 methyltransferase Set1 is involved in maintenance of ergosterol homeostasis and resistance to Brefeldin A"],"prefix":"10.1073","volume":"110","author":[{"given":"Paul F.","family":"South","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla 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