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Yeast epigenetics

Sun-Ju Yi, Kyunghwan Kim
Chromatin is an intelligent building block that can express either external or internal needs through structural changes. To date, three methods to change chromatin structure and regulate gene expression have been well-documented: histone modification, histone exchange, and ATP-dependent chromatin remodeling. Recently, a growing body of literature has suggested that histone tail cleavage is related to various cellular processes including stem cell differentiation, osteoclast differentiation, granulocyte differentiation, mammary gland differentiation, viral infection, aging, and yeast sporulation...
March 15, 2018: BMB Reports
Jiang Li, Caili Li, Shanfa Lu
Cytosine DNA methylation is highly conserved epigenetic modification involved in a wide range of biological processes in eukaryotes. It was established and maintained by cytosine-5 DNA methyltransferases (C5-MTases) in plants. Through genome-wide identification, eight putative SmC5-MTase genes were identified from the genome of Salvia miltiorrhiza , a well-known traditional Chinese medicine material and an emerging model medicinal plant. Based on conserved domains and phylogenetic analysis, eight SmC5-MTase genes were divided into four subfamilies, including MET , CMT , DRM and DNMT2 ...
2018: PeerJ
Liangping Su, Hongyuan Li, Cheng Huang, Tingting Zhao, Yongjun Zhang, Xueqing Ba, Zhongwei Li, Yu Zhang, Baiqu Huang, Jun Lu, Yanmei Zhao, Xiaoxue Li
Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3) in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway...
March 6, 2018: Cell Reports
Yunfang Meng, Yumeng Fan, Wanqing Liao, Xiaorong Lin
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, are first identified in plants and are known to be involved in reading and effecting chromatin modification...
March 2, 2018: Applied and Environmental Microbiology
Stephen Frenk, Jonathan Houseley
Ageing leads to dramatic changes in the physiology of many different tissues resulting in a spectrum of pathology. Nonetheless, many lines of evidence suggest that ageing is driven by highly conserved cell intrinsic processes, and a set of unifying hallmarks of ageing has been defined. Here, we survey reports of age-linked changes in basal gene expression across eukaryotes from yeast to human and identify six gene expression hallmarks of cellular ageing: downregulation of genes encoding mitochondrial proteins; downregulation of the protein synthesis machinery; dysregulation of immune system genes; reduced growth factor signalling; constitutive responses to stress and DNA damage; dysregulation of gene expression and mRNA processing...
February 28, 2018: Biogerontology
Elizabeth Delorme-Axford, Daniel J Klionsky
Autophagy is a highly conserved catabolic pathway that is vital for development, cell survival and the degradation of dysfunctional organelles and toxic aggregates. Dysregulation of autophagy is associated with cancer, neurodegeneration and lysosomal storage diseases. Accordingly, autophagy is precisely regulated at multiple levels (transcriptional, post-transcriptional, epigenetic, translational and post-translational) to prevent aberrant activity. Various model organisms exist to study autophagy but the baker's yeast Saccharomyces cerevisiae continues to be very advantageous for genetic and biochemical analysis of non-selective and selective autophagy...
January 25, 2018: Journal of Biological Chemistry
Daniel Jost, Cédric Vaillant
Recent progresses of genome-wide chromatin conformation capture techniques have shown that the genome is segmented into hierarchically organized spatial compartments. However, whether this non-random 3D organization only reflects or indeed contributes-and how-to the regulation of genome function remain to be elucidated. The observation in many species that 3D domains correlate strongly with the 1D epigenomic information along the genome suggests a dynamic coupling between chromatin organization and epigenetic regulation...
January 22, 2018: Nucleic Acids Research
Karen Chen, Seth A Bennett, Navin Rana, Huda Yousuf, Mohamed Said, Sadiqa Taaseen, Natalie Mendo, Steven M Meltser, Mariana P Torrente
Amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) are devastating neurodegenerative diseases involving the progressive degeneration of neurons. No cure is available for patients diagnosed with these diseases. A prominent feature of both ALS and PD is the accumulation of protein inclusions in the cytoplasm of degenerating neurons; however, the particular proteins constituting these inclusions vary: the RNA-binding proteins TDP-43 and FUS are most notable in ALS, while α-synuclein aggregates into Lewy bodies in PD...
January 8, 2018: ACS Chemical Neuroscience
Upendarrao Golla, Swati Swagatika, Sakshi Chauhan, Raghuvir Singh Tomar
KP1019 ([trans-RuCl4 (1H-indazole)2 ]; FFC14A) is one of the promising ruthenium-based anticancer drugs undergoing clinical trials. Despite the pre-clinical and clinical success of KP1019, the mode of action and various factors capable of modulating its effects are largely unknown. Here, we used transcriptomics and genetic screening approaches in budding yeast model and deciphered various genetic targets and plethora of cellular pathways including cellular signaling, metal homeostasis, vacuolar transport, and lipid homeostasis that are primarily targeted by KP1019...
November 17, 2017: Oncotarget
Leonie Johanna Jahn, Bethany Mason, Peter Brøgger, Tea Toteva, Dennis Kim Nielsen, Genevieve Thon
Chromatin structure regulates both genome expression and dynamics in eukaryotes, where large heterochromatic regions are epigenetically silenced through the methylation of histone H3K9, histone deacetylation, and the assembly of repressive complexes. Previous genetic screens with the fission yeast Schizosaccharomyces pombe have led to the identification of key enzymatic activities and structural constituents of heterochromatin. We report here on additional factors discovered by screening a library of deletion mutants for silencing defects at the edge of a heterochromatic domain bound by its natural boundary-the IR-R + element-or by ectopic boundaries...
February 2, 2018: G3: Genes—Genomes—Genetics
Varun Sood, Jason H Brickner
Certain genes show more rapid reactivation for several generations following repression, a conserved phenomenon called epigenetic transcriptional memory. Following previous growth in galactose, GAL gene transcriptional memory confers a strong fitness benefit in Saccharomyces cerevisiae adapting to growth in galactose for up to 8 generations. A genetic screen for mutants defective for GAL gene memory revealed new insights into the molecular mechanism, adaptive consequences, and evolutionary history of memory...
December 4, 2017: Current Biology: CB
Grigory Sharov, Karine Voltz, Alexandre Durand, Olga Kolesnikova, Gabor Papai, Alexander G Myasnikov, Annick Dejaegere, Adam Ben Shem, Patrick Schultz
The transcription co-activator complex SAGA is recruited to gene promoters by sequence-specific transcriptional activators and by chromatin modifications to promote pre-initiation complex formation. The yeast Tra1 subunit is the major target of acidic activators such as Gal4, VP16, or Gcn4 but little is known about its structural organization. The 430 kDa Tra1 subunit and its human homolog the transformation/transcription domain-associated protein TRRAP are members of the phosphatidyl 3-kinase-related kinase (PIKK) family...
November 16, 2017: Nature Communications
Gregory A Newby, Susan Lindquist
To thrive in an ever-changing environment, microbes must widely distribute their progeny to colonize new territory. Simultaneously, they must evolve and adapt to the stresses of unpredictable surroundings. In both of these regards, diversity is key-if an entire population moved together or responded to the environment in the same way, it could easily go extinct. Here, we show that the epigenetic prion switch [SWI+] establishes a specialized subpopulation with a "pioneer" phenotypic program in Saccharomyces cerevisiae...
November 2017: PLoS Biology
Soazik P Jamin, Fabrice G Petit, Christine Kervarrec, Fatima Smagulova, Doris Illner, Harry Scherthan, Michael Primig
EXOSC10 is a catalytic subunit of the exosome that processes biologically active transcripts, degrades aberrant mRNAs and targets certain long non-coding RNAs (lncRNAs). The yeast orthologue Rrp6 is required for efficient growth and gametogenesis, and becomes unstable during meiosis. However, nothing is known about the localization, stability and function of EXOSC10 in the rodent male germline. We detect the protein in nucleoli and the cytoplasm of mitotic and meiotic germ cells, and find that it transiently associates with the XY body, a structure targeted by meiotic sex chromosome inactivation (MSCI)...
November 8, 2017: Scientific Reports
Haijin He, Yang Li, Qianhua Dong, An-Yun Chang, Feng Gao, Zhongxuan Chi, Min Su, Faben Zhang, Hyoju Ban, Rob Martienssen, Yu-Hang Chen, Fei Li
During DNA replication, chromatin is disrupted ahead of the replication fork, and epigenetic information must be restored behind the fork. How epigenetic marks are inherited through DNA replication remains poorly understood. Histone H3 lysine 9 (H3K9) methylation and histone hypoacetylation are conserved hallmarks of heterochromatin. We previously showed that the inheritance of H3K9 methylation during DNA replication depends on the catalytic subunit of DNA polymerase epsilon, Cdc20. Here we show that the histone-fold subunit of Pol epsilon, Dpb4, interacts an uncharacterized small histone-fold protein, SPCC16C4...
November 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
Xiucai Pan, Yuan Fang, Xueming Yang, Dongyang Zheng, Lifen Chen, Lei Wang, Jin Xiao, Xiu-E Wang, Kai Wang, Zhukuan Cheng, Hengxiu Yu, Wenli Zhang
BACKGROUND: The role of histone modifications in the DNA damage response has been extensively studied in non-plant systems, including mammals and yeast. However, there is a lack of detailed evidence showing how chromatin dynamics, either an individual mark or combined chromatin states, participate in regulating differentially expressed genes in the plant DNA damage response. RESULTS: In this study, we used RNA-seq and ChIP-seq to show that differentially expressed genes (DEGs), in response to ionizing radiation (IR), might be involved in different pathways responsible for the DNA damage response...
October 12, 2017: BMC Genomics
Cecily E Allen, Mark A Doll, David W Hein
Hydralazine is used in the treatment of essential hypertension and is under investigation for epigenetic therapy in the treatment of neoplastic and renal diseases. N -acetyltransferase (NAT) 2 exhibits a common genetic polymorphism in human populations. After recombinant expression in yeast, human NAT2 exhibited an apparent Lineweaver-Burk constant ( K- m ) value (20.1 ± 8.8 μ M) for hydralazine over 20-fold lower than the apparent K- m value (456 ± 57 μ M) for recombinant human NAT1 ( P = 0.0016). The apparent V max value for recombinant human NAT1 (72...
December 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Hua Zhang, Yu Zhao, Dao-Xiu Zhou
Sirtuins, a family of proteins with homology to the yeast silent information regulator 2 (Sir2), are NAD+-dependent histone deacetylases and play crucial roles in energy sensing and regulation in yeast and animal cells. Plants are autotrophic organisms and display distinct features of carbon and energy metabolism. It remains largely unexplored whether and how plant cells sense energy/redox status to control carbon metabolic flux under various growth conditions. In this work, we show that the rice nuclear sirtuin OsSRT1 not only functions as an epigenetic regulator to repress glycolytic genes expression and glycolysis in seedlings, but also inhibits transcriptional activity of glyceraldehyde-3-phosphatedehydrogenase (GAPDH) that is enriched on glycolytic genes promoters and stimulates their expression...
December 1, 2017: Nucleic Acids Research
Wei Wang, Liang Xu, Lulu Hu, Jenny Chong, Chuan He, Dong Wang
N(6)-Methyladenine (N(6)-mA or 6 mA) is an epigenetic DNA modification in eukaryotic genomes. In contrast to the well-established roles of 5-methylcytosine for epigenetic regulation of gene expression, the functional roles of N(6)-mA remain elusive. In particular, the impact of N(6)-mA modification of the DNA template on RNA polymerase II (pol II) transcription elongation is not known. In this work, using the Saccharomyces cerevisiae pol II transcriptional elongation system as a model, we investigated the molecular mechanism of pol II recognition and processing of N(6)-mA sites via both biochemical and structural approaches...
October 3, 2017: Journal of the American Chemical Society
Adam H Tencer, Jovylyn Gatchalian, Brianna J Klein, Abid Khan, Yi Zhang, Brian D Strahl, Karel H M van Wely, Tatiana G Kutateladze
The protein partner of Sans-fille (PPS) and its human homolog DIDO mediate diverse chromatin activities, including the regulation of stemness genes in embryonic stem cells and splicing in Drosophila. Here, we show that the PHD fingers of PPS and DIDO recognize the histone mark H3K4me3 in a pH-dependent manner: the binding is enhanced at high pH values but is decreased at low pH. Structural analysis reveals that the pH dependency is due to the presence of a histidine residue in the K4me3-binding aromatic cage of PPS...
October 3, 2017: Structure
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