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Appl Environ Microbiol

Title:		Plant Homeodomain Genes Play Important Roles in Cryptococcal Yeast-Hypha Transition
Author(s):		Meng Y; Fan Y; Liao W; Lin X;
Address:		"Department of Dermatology, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, China. Department of Biology, Texas A&M University, College Station, Texas, USA. Department of Dermatology and Venereology, Changzheng Hospital, Shanghai, China. Department of Microbiology, University of Georgia, Athens, Georgia, USA. Department of Dermatology and Venereology, Changzheng Hospital, Shanghai, China liaowanqing@sohu.com Xiaorong.Lin@uga.edu. Department of Biology, Texas A&M University, College Station, Texas, USA liaowanqing@sohu.com Xiaorong.Lin@uga.edu"
Journal Title:		Appl Environ Microbiol
Year:		2018
Volume:		20180416
Issue:		9
Page Number:		-
DOI:		10.1128/AEM.01732-17
ISSN/ISBN:		1098-5336 (Electronic) 0099-2240 (Print) 0099-2240 (Linking)
Abstract:		"Cryptococcus neoformans is a major opportunistic fungal pathogen. Like many dimorphic fungal pathogens, C. neoformans 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 Cryptococcus mating and yeast-hypha transition. We found 16 PHD finger domains distributed among 15 genes in the Cryptococcus genome, with two genes, ZNF1alpha and RUM1alpha, 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 rum1alphaDelta and znf1alphaDelta mutants showed enhanced ability to initiate filamentation but impaired ability to maintain filamentous growth. The bye1Delta and the phd11Delta mutants exhibited enhanced filamentation, while the set302Delta 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 C. neoformansIMPORTANCE Morphotype is known to have a profound impact on cryptococcal interaction with various hosts, including mammalian hosts. The yeast form of Cryptococcus neoformans 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 C. neoformans, we investigated the roles of the 15 PHD finger genes in Cryptococcus 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"
Keywords:		"Amino Acid Sequence Cryptococcus neoformans/genetics/*growth & development Epigenesis, Genetic/genetics Genes, Plant/*genetics Homeodomain Proteins/*genetics/metabolism Hyphae/*genetics/growth & development Morphogenesis/*genetics Sequence Alignment dimor;"
Notes:		"MedlineMeng, Yunfang Fan, Yumeng Liao, Wanqing Lin, Xiaorong eng R01 AI097599/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2018/03/04 Appl Environ Microbiol. 2018 Apr 16; 84(9):e01732-17. doi: 10.1128/AEM.01732-17. Print 2018 May 1"