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On the other hand, histone methylation is a regulatory mechanism with pleiotropic effects, including the virulence of several pathogenic fungi. However, the role of epigenetic changes at the histone level never has been studied in <jats:italic>Mucorales<\/jats:italic>. Here, we dissected the functional role of Set1, a histone methyltransferase that catalyzes the methylation of H3K4, which is associated with the activation of gene transcription and virulence. A comparative analysis of the <jats:italic>Mucor lusitanicus<\/jats:italic> genome (previously known as <jats:italic>Mucor circinelloides<\/jats:italic> f. <jats:italic>lusitanicus<\/jats:italic>) identified only one homolog of Set1 from <jats:italic>Candida albicans<\/jats:italic> and <jats:italic>Saccharomyces cerevisiae<\/jats:italic> that contains the typical SET domain. Knockout strains in the gene <jats:italic>set1<\/jats:italic> lacked H3K4 monomethylation, dimethylation, and trimethylation enzymatic activities. These strains also showed a significant reduction in vegetative growth and sporulation. Additionally, <jats:italic>set1<\/jats:italic> null strains were more sensitive to SDS, EMS, and UV light, indicating severe impairment in the repair process of the cell wall and DNA lesions and a correlation between Set1 and these processes. During pathogen-host interactions, strains lacking the <jats:italic>set1<\/jats:italic> gene exhibited shortened polar growth within the phagosome and attenuated virulence both in vitro and in vivo. Our findings suggest that the histone methyltransferase Set1 coordinates several cell processes related to the pathogenesis of <jats:italic>M. lusitanicus<\/jats:italic> and may be an important target for future therapeutic strategies against mucormycosis.<\/jats:p>","DOI":"10.1186\/s43008-023-00136-3","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:03:54Z","timestamp":1710374634000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["H3K4 methylation regulates development, DNA repair, and virulence in Mucorales"],"prefix":"10.3897","volume":"15","author":[{"given":"Macario","family":"Osorio-Concepci\u00f3n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Lax","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damaris","family":"Lorenzo-Guti\u00e9rrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Tom\u00e1s","family":"C\u00e1novas-M\u00e1rquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghizlane","family":"Tahiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eusebio","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Binder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Esteban","family":"Nicol\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7605-1726","authenticated-orcid":false,"given":"Victoriano","family":"Garre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2258","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"key":"136_CR1","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/nrg.2016.59","volume":"17","author":"CD Allis","year":"2016","unstructured":"Allis CD, Jenuwein T (2016) The molecular hallmarks of epigenetic control. 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