{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T16:14:32Z","timestamp":1761581672752,"version":"3.41.2"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI097599"],"award-info":[{"award-number":["R01AI097599"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["1012445"],"award-info":[{"award-number":["1012445"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002860","name":"China Sponsorship Council","doi-asserted-by":"publisher","award":["201306580029"],"award-info":[{"award-number":["201306580029"]}],"id":[{"id":"10.13039\/501100002860","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            is a major opportunistic fungal pathogen. Like many dimorphic fungal pathogens,\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            can undergo morphological transition from the yeast form to the hypha form, and its morphotype is tightly linked to its virulence. Although some genetic factors controlling morphogenesis have been identified, little is known about the epigenetic regulation in this process. Proteins with the plant homeodomain (PHD) finger, a structurally conserved domain in eukaryotes, were first identified in plants and are known to be involved in reading and effecting chromatin modification. Here, we investigated the role of the PHD finger family genes in\n            <jats:named-content content-type=\"genus-species\">Cryptococcus<\/jats:named-content>\n            mating and yeast-hypha transition. We found 16 PHD finger domains distributed among 15 genes in the\n            <jats:named-content content-type=\"genus-species\">Cryptococcus<\/jats:named-content>\n            genome, with two genes,\n            <jats:italic>ZNF1<\/jats:italic>\n            \u03b1 and\n            <jats:italic>RUM1<\/jats:italic>\n            \u03b1, located in the mating type locus. We deleted these 15 PHD genes and examined the impact of their disruption on cryptococcal morphogenesis. The deletion of five PHD finger genes dramatically affected filamentation. The\n            <jats:italic>rum1<\/jats:italic>\n            \u03b1\u0394 and\n            <jats:italic>znf1<\/jats:italic>\n            \u03b1\u0394 mutants showed enhanced ability to initiate filamentation but impaired ability to maintain filamentous growth. The\n            <jats:italic>bye1<\/jats:italic>\n            \u0394 and the\n            <jats:italic>phd11<\/jats:italic>\n            \u0394 mutants exhibited enhanced filamentation, while the\n            <jats:italic>set302<\/jats:italic>\n            \u0394 mutants displayed reduced filamentation. Ectopic overexpression of these five genes in the corresponding null mutants partially or completely restored the defect in filamentation. Furthermore, we demonstrated that Phd11, a suppressor of filamentation, regulates the yeast-hypha transition through the known master regulator Znf2. The findings indicate the importance of epigenetic regulation in controlling dimorphic transition in\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            .\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Morphotype is known to have a profound impact on cryptococcal interaction with various hosts, including mammalian hosts. The yeast form of\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            is considered the virulent form, while its hyphal form is attenuated in mammalian models of cryptococcosis. Although some genetic regulators critical for cryptococcal morphogenesis have been identified, little is known about epigenetic regulation in this process. Given that plant homeodomain (PHD) finger proteins are involved in reading and effecting chromatin modification and their functions are unexplored in\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            , we investigated the roles of the 15 PHD finger genes in\n            <jats:named-content content-type=\"genus-species\">Cryptococcus<\/jats:named-content>\n            mating and yeast-hypha transition. Five of them profoundly affect filamentation as either a suppressor or an activator. Phd11, a suppressor of filamentation, regulates this process via Znf2, a known master regulator of morphogenesis. Thus, epigenetic regulation, coupled with genetic regulation, controls this yeast-hypha transition event.\n          <\/jats:p>","DOI":"10.1128\/aem.01732-17","type":"journal-article","created":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T11:11:28Z","timestamp":1519816288000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Plant Homeodomain Genes Play Important Roles in Cryptococcal Yeast-Hypha Transition"],"prefix":"10.1128","volume":"84","author":[{"given":"Yunfang","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Dermatology, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, China"},{"name":"Department of Biology, Texas A&amp;M University, College Station, Texas, USA"},{"name":"Department of Dermatology and Venereology, Changzheng Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumeng","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Biology, Texas A&amp;M University, College Station, Texas, USA"},{"name":"Department of Microbiology, University of Georgia, Athens, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanqing","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Changzheng Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3390-8387","authenticated-orcid":false,"given":"Xiaorong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biology, Texas A&amp;M University, College Station, Texas, USA"},{"name":"Department of Microbiology, University of Georgia, Athens, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328322ffac"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30243-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003027"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a019794"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01433-15"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002765"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.2307\/3758800"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.06.011"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1245"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03563.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000953"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00259-13"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.1.5.704-718.2002"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.1.3.366-377.2002"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020384"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.1.3.432-439.2002"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2011.02.001"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1041402"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-313X.1993.04010137.x"},{"key":"e_1_3_3_21_2","first-page":"364","article-title":"The PHD finger: a versatile epigenome reader","volume":"36","author":"Sanchez R","year":"2011","unstructured":"Sanchez R, Zhou M-M. 2011. 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