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Fungi epigenetics

Walter H Moos, Carl A Pinkert, Michael H Irwin, Douglas V Faller, Krishna Kodukula, Ioannis P Glavas, Kosta Steliou
Preclinical Research Approximately 2,500 years ago, Hippocrates used the word herpes as a medical term to describe lesions that appeared to creep or crawl on the skin, advocating heat as a possible treatment. During the last 50 years, pharmaceutical research has made great strides, and therapeutic options have expanded to include small molecule antiviral agents, protease inhibitors, preventive vaccines for a handful of the papillomaviruses, and even cures for hepatitis C virus infections. However, effective treatments for persistent and recurrent viral infections, particularly the highly prevalent herpesviruses, continue to represent a significant unmet medical need, affecting the majority of the world's population...
October 20, 2016: Drug Development Research
Juliane Macheleidt, Derek J Mattern, Juliane Fischer, Tina Netzker, Jakob Weber, Volker Schroeckh, Vito Valiante, Axel A Brakhage
Fungi have the capability to produce a tremendous number of so-called secondary metabolites, which possess a multitude of functions, e.g., communication signals during coexistence with other microorganisms, virulence factors during pathogenic interactions with plants and animals, and in medical applications. Therefore, research on this topic has intensified significantly during the past 10 years and thus knowledge of regulatory mechanisms and the understanding of the role of secondary metabolites have drastically increased...
October 5, 2016: Annual Review of Genetics
Matthew Z Anderson, Allison M Porman, Na Wang, Eugenio Mancera, Denis Huang, Christina A Cuomo, Richard J Bennett
Heritable epigenetic changes underlie the ability of cells to differentiate into distinct cell types. Here, we demonstrate that the fungal pathogen Candida tropicalis exhibits multipotency, undergoing stochastic and reversible switching between three cellular states. The three cell states exhibit unique cellular morphologies, growth rates, and global gene expression profiles. Genetic analysis identified six transcription factors that play key roles in regulating cell differentiation. In particular, we show that forced expression of Wor1 or Efg1 transcription factors can be used to manipulate transitions between all three cell states...
October 2016: PLoS Genetics
Hsin-Yu Ho, Chiao-Wen Lin, Ming-Hsien Chien, Russel J Reiter, Shih-Chi Su, Yi-Hsien Hsieh, Shun-Fa Yang
Nasopharyngeal carcinoma (NPC), a disease common in the South-East Asian population, has high lymph node metastatic ability. Melatonin, an endogenously produced substance present in animals, plants, fungi, and bacteria, has oncotstatic activity via several mechanisms. The molecular mechanisms involved in melatonin-mediated tumor inhibitory potential are not completely defined. Here, we show that melatonin treatment inhibits TPA-induced cell motility by regulating matrix metalloproteinase-9 (MMP-9) expression in NPC...
September 7, 2016: Journal of Pineal Research
John Slattery, Derrick F MacFabe, Stephen G Kahler, Richard E Frye
BACKGROUND: Many lines of scientific research suggest that Autism Spectrum Disorders (ASDs) may be associated with alterations in the enteric ecosystem, including alterations of the enteric macrobiome (i.e. helminthes and fungi) and changes in predominant microbiome species, particularly a reduction in microbiome diversity. METHODS: We performed and comprehensive review of the literature and summarized the major findings. RESULTS: These alterations are believed to be due to a variety of factors including changes in the post-industrial society related to decreased exposure to symbiotic organisms, increased human migration, overuse of antibiotics and changes in dietary habits...
September 5, 2016: Current Pharmaceutical Design
Aisling Y Coughlan, Sara J Hanson, Kevin P Byrne, Kenneth H Wolfe
Centromere organization has evolved dramatically in one clade of fungi, the Saccharomycotina. These yeasts have lost the ability to make normal eukaryotic heterochromatin with histone H3K9 methylation, which is a major component of pericentromeric regions in other eukaryotes. Following this loss, several different types of centromere emerged, including two types of sequence-defined ("point") centromeres, and the epigenetically defined "small regional" centromeres of Candida albicans Here we report that centromeres of the methylotrophic yeast Komagataella phaffii (formerly called Pichia pastoris) are structurally defined...
2016: Genome Biology and Evolution
Qian Zhang, Longfei Chen, Xi Yu, Heng Liu, Oren Akhberdi, Jiao Pan, Xudong Zhu
In filamentous fungi, many gene clusters for the biosynthesis of secondary metabolites often stay silent under laboratory culture conditions because of the absence of communication with its natural environment. Epigenetic processes have been demonstrated to be critical in the expression of the genes or gene clusters. Here, we report the identification of a B-type histone acetyltransferase, Hat1, and demonstrate its significant roles in secondary metabolism, conidiation, and the cell wall integrity in the fungus Pestalotiopsis microspora...
July 11, 2016: Journal of Basic Microbiology
Wai-Shin Yong, Fei-Man Hsu, Pao-Yang Chen
DNA methylation is an epigenetic modification that plays an important role in regulating gene expression and therefore a broad range of biological processes and diseases. DNA methylation is tissue-specific, dynamic, sequence-context-dependent and trans-generationally heritable, and these complex patterns of methylation highlight the significance of profiling DNA methylation to answer biological questions. In this review, we surveyed major methylation assays, along with comparisons and biological examples, to provide an overview of DNA methylation profiling techniques...
2016: Epigenetics & Chromatin
Elisabetta Levati, Sara Sartini, Angelo Bolchi, Simone Ottonello, Barbara Montanini
Moonlighting proteins, including metabolic enzymes acting as transcription factors (TF), are present in a variety of organisms but have not been described in higher fungi so far. In a previous genome-wide analysis of the TF repertoire of the plant-symbiotic fungus Tuber melanosporum, we identified various enzymes, including the sulfur-assimilation enzyme phosphoadenosine-phosphosulfate reductase (PAPS-red), as potential transcriptional activators. A functional analysis performed in the yeast Saccharomyces cerevisiae, now demonstrates that a specific variant of this enzyme, PAPS-red A, localizes to the nucleus and is capable of transcriptional activation...
2016: Scientific Reports
Yuan Sun, Christine Gadoury, Matthew P Hirakawa, Richard J Bennett, Doreen Harcus, Anne Marcil, Malcolm Whiteway
UNLABELLED: It has been proposed that the ancestral fungus was mating competent and homothallic. However, many mating-competent fungi were initially classified as asexual because their mating capacity was hidden behind layers of regulation. For efficient in vitro mating, the essentially obligate diploid ascomycete pathogen Candida albicans has to change its mating type locus from heterozygous MTLa/α to homozygous MTLa/a or MTLα/α and then undergo an environmentally controlled epigenetic switch to the mating-competent opaque form...
2016: MBio
V O Shlyakhovenko
In the review, the use of the ribonucleases for cancer therapy is discussed. Using of epigenetic mechanisms of regulation--blocking protein synthesis without affecting the DNA structure--is a promising direction in the therapy. The ribonucleases isolated from different sources, despite of similar mechanism of enzymatic reactions, have different biological effects. The use of enzymes isolated from new sources, particularly from plants and fungi, shows promising results. In this article we discuss the new approach for the use of enzymes resistant to inhibitors and ribozymes, that is aimed at the destruction of the oncogene specific mRNA and the induction of apoptosis...
March 2016: Experimental Oncology
Kunlong Yang, Linlin Liang, Fanlei Ran, Yinghang Liu, Zhenguo Li, Huahui Lan, Peili Gao, Zhenhong Zhuang, Feng Zhang, Xinyi Nie, Shimuye Kalayu Yirga, Shihua Wang
DNA methylation is essential for epigenetic regulation of gene transcription and development in many animals, plants and fungi. We investigated whether DNA methylation plays a role in the development and secondary metabolism of Aspergillus flavus, identified the DmtA methyltransferase from A. flavus, and produced a dmtA knock-out mutant by replacing the dmtA coding sequence with the pyrG selectable marker. The A. flavus dmtA null mutant lines produced white fluffy mycelium in liquid medium, and displayed a slightly flavescent conidial pigmentation compared with the normal yellow of the wild-type strain when grown on agar...
2016: Scientific Reports
Michael Freitag
Chromosome segregation relies on coordinated activity of a large assembly of proteins, the kinetochore interaction network (KIN). How conserved the underlying mechanisms driving the epigenetic phenomenon of centromere and kinetochore assembly and maintenance are remains unclear, even though various eukaryotic models have been studied. More than 50 different proteins, many in multiple copies, comprise the KIN or are associated with fungal centromeres and kinetochores. Proteins isolated from immune sera recognized centromeric regions on chromosomes and thus were named centromere proteins (CENPs)...
May 2016: Mycologia
Víctor González-Menéndez, Mercedes Pérez-Bonilla, Ignacio Pérez-Victoria, Jesús Martín, Francisca Muñoz, Fernando Reyes, José R Tormo, Olga Genilloud
Small molecule histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors are commonly used to perturb the production of fungal metabolites leading to the induction of the expression of silent biosynthetic pathways. Several reports have described the variable effects observed in natural product profiles in fungi treated with HDAC and DNMT inhibitors, such as enhanced chemical diversity and/or the induction of new molecules previously unknown to be produced by the strain. Fungal endophytes are known to produce a wide variety of secondary metabolites (SMs) involved in their adaptation and survival within higher plants...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
S S El-Hawary, R Mohammed, S F AbouZid, W Bakeer, R Ebel, A M Sayed, M E Rateb
AIMS: The aim was to isolate, identify and characterize endophytes from Solanum nigrum L. as a new source of the cytotoxic steroidal alkaloid solamargine. METHODS AND RESULTS: Three endophytic fungi; SNFSt, SNFL and SNFF were isolated from S. nigrum and identified by molecular methods. Preliminary TLC screening showed a common metabolite between the plant and one of these fungi, SNFSt which was identified as Aspergillus flavus based on the phylogenetic analysis of its ITS sequence...
April 2016: Journal of Applied Microbiology
Guohong Liu, Christopher Q Weston, Long K Pham, Shannon Waltz, Helen Barnes, Paula King, Dan Sphar, Robert T Yamamoto, R Allyn Forsyth
We describe continuing work to develop restriction endonucleases as tools to enrich targeted genomes of interest from diverse populations. Two approaches were developed in parallel to segregate genomic DNA based on cytosine methylation. First, the methyl-sensitive endonuclease HpaII was used to bind non-CG methylated DNA. Second, a truncated fragment of McrB was used to bind CpG methylated DNA. Enrichment levels of microbial genomes can exceed 100-fold with HpaII allowing improved genomic detection and coverage of otherwise trace microbial genomes from sputum...
2016: PloS One
Yu-long Wang, Zhang-xun Wang, Chun Liu, Si-bao Wang, Bo Huang
DNA methylation is a basic epigenetic mechanism found in eukaryotes, but its patterns and roles vary significantly among diverse taxa. In fungi, DNA methylation has various effects on diverse biological processes. However, its function in the sexual development of fungi remains unclear. Cordyceps militaris, readily performs sexual reproduction and thus provides a remarkably rich model for understanding epigenetic processes in sexual development. Here, we surveyed the methylome of C. militaris at single-base resolution to assess DNA methylation patterns during sexual development using genomic bisulfite sequencing (BS-Seq)...
December 2015: Fungal Biology
Daniela Elena Serban
Inflammatory bowel disease (IBD), including ulcerative colitis, Crohn's disease, and unclassified IBD, continues to cause significant morbidity. While its incidence is increasing, no clear etiology and no cure have yet been discovered. Recent findings suggest that IBD may have a multifactorial etiology, where complex interactions between genetics, epigenetics, environmental factors (including diet but also infections, antibiotics, and sanitation), and host immune system lead to abnormal immune responses and chronic inflammation...
December 2015: Nutrition in Clinical Practice
Jiamu Du, Lianna M Johnson, Steven E Jacobsen, Dinshaw J Patel
Methylation of DNA and of histone 3 at Lys 9 (H3K9) are highly correlated with gene silencing in eukaryotes from fungi to humans. Both of these epigenetic marks need to be established at specific regions of the genome and then maintained at these sites through cell division. Protein structural domains that specifically recognize methylated DNA and methylated histones are key for targeting enzymes that catalyse these marks to appropriate genome sites. Genetic, genomic, structural and biochemical data reveal connections between these two epigenetic marks, and these domains mediate much of the crosstalk...
September 2015: Nature Reviews. Molecular Cell Biology
Monika Hilker, Jens Schwachtje, Margarete Baier, Salma Balazadeh, Isabel Bäurle, Sven Geiselhardt, Dirk K Hincha, Reinhard Kunze, Bernd Mueller-Roeber, Matthias C Rillig, Jens Rolff, Tina Romeis, Thomas Schmülling, Anke Steppuhn, Joost van Dongen, Sarah J Whitcomb, Susanne Wurst, Ellen Zuther, Joachim Kopka
Experience and memory of environmental stimuli that indicate future stress can prepare (prime) organismic stress responses even in species lacking a nervous system. The process through which such organisms prepare their phenotype for an improved response to future stress has been termed 'priming'. However, other terms are also used for this phenomenon, especially when considering priming in different types of organisms and when referring to different stressors. Here we propose a conceptual framework for priming of stress responses in bacteria, fungi and plants which allows comparison of priming with other terms, e...
August 20, 2015: Biological Reviews of the Cambridge Philosophical Society
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