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Yeast epigenetics

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https://www.readbyqxmd.com/read/29146944/structure-of-the-transcription-activator-target-tra1-within-the-chromatin-modifying-complex-saga
#1
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
https://www.readbyqxmd.com/read/29135981/pioneer-cells-established-by-the-swi-prion-can-promote-dispersal-and-out-crossing-in-yeast
#2
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
https://www.readbyqxmd.com/read/29118343/exosc10-rrp6-is-post-translationally-regulated-in-male-germ-cells-and-controls-the-onset-of-spermatogenesis
#3
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
https://www.readbyqxmd.com/read/29109278/coordinated-regulation-of-heterochromatin-inheritance-by-dpb3-dpb4-complex
#4
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 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29025389/chromatin-states-responsible-for-the-regulation-of-differentially-expressed-genes-under-60-co-%C3%AE-ray-radiation-in-rice
#5
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
https://www.readbyqxmd.com/read/29018032/n-acetyltransferase-2-genotype-dependent-n-acetylation-of-hydralazine-in-human-hepatocytes
#6
Cecily E Allen, Mark A Doll, David W Hein
Hydralazine is used in treatment of essential hypertension and is under investigation for epigenetic therapy in the treatment of neoplastic and renal diseases. N-acetyltransferase 2 (NAT2) exhibits a common genetic polymorphism in human populations. Following recombinant expression in yeast, human NAT2 exhibited an apparent Km (20.1 ± 8.8 μM) for hydralazine over 20-fold lower than the apparent Km (456 ± 57 μM) for recombinant human NAT1 (p=0.0016). The apparent Vmax for recombinant human NAT1 (72.2 ± 17...
October 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28981755/rice-nad-dependent-histone-deacetylase-ossrt1-represses-glycolysis-and-regulates-the-moonlighting-function-of-gapdh-as-a-transcriptional-activator-of-glycolytic-genes
#7
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...
September 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28933854/epigenetic-dna-modification-n-6-methyladenine-causes-site-specific-rna-polymerase-ii-transcriptional-pausing
#8
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
https://www.readbyqxmd.com/read/28919441/a-unique-ph-dependent-recognition-of-methylated-histone-h3k4-by-pps-and-dido
#9
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
https://www.readbyqxmd.com/read/28904333/the-ino80-complex-mediates-epigenetic-centromere-propagation-via-active-removal-of-histone-h3
#10
Eun Shik Choi, Youngseo Cheon, Keunsoo Kang, Daeyoup Lee
The centromere is the chromosomal locus at which the kinetochore is assembled to direct chromosome segregation. The histone H3 variant, centromere protein A (CENP-A), is known to epigenetically mark active centromeres, but the mechanism by which CENP-A propagates at the centromere, replacing histone H3, remains poorly understood. Using fission yeast, here we show that the Ino80 adenosine triphosphate (ATP)-dependent chromatin-remodeling complex, which removes histone H3-containing nucleosomes from associated chromatin, promotes CENP-A(Cnp1) chromatin assembly at the centromere in a redundant manner with another chromatin-remodeling factor Chd1(Hrp1)...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28903324/the-pwwp-domain-of-the-human-oncogene-whsc1l1-nsd3-induces-a-metabolic-shift-toward-fermentation
#11
Germana B Rona, Diego S G Almeida, Anderson S Pinheiro, Elis C A Eleutherio
WHSC1L1/NSD3, one of the most aggressive human oncogenes, has two isoforms derived from alternative splicing. Overexpression of long or short NSD3 is capable of transforming a healthy into a cancer cell. NSD3s, the short isoform, contains only a PWWP domain, a histone methyl-lysine reader involved in epigenetic regulation of gene expression. With the aim of understanding the NSD3s PWWP domain role in tumorigenesis, we used Saccharomyces cerevisiae as an experimental model. We identified the yeast protein Pdp3 that contains a PWWP domain that closely resembles NSD3s PWWP...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28841138/aneuploidy-as-a-cause-of-impaired-chromatin-silencing-and-mating-type-specification-in-budding-yeast
#12
Wahid A Mulla, Chris W Seidel, Jin Zhu, Hung-Ji Tsai, Sarah E Smith, Pushpendra Singh, William D Bradford, Scott McCroskey, Anjali R Nelliat, Juliana Conkright, Allison Peak, Kathryn E Malanowski, Anoja G Perera, Rong Li
Aneuploidy and epigenetic alterations have long been associated with carcinogenesis, but it was unknown whether aneuploidy could disrupt the epigenetic states required for cellular differentiation. In this study, we found that ~3% of random aneuploid karyotypes in yeast disrupt the stable inheritance of silenced chromatin during cell proliferation. Karyotype analysis revealed that this phenotype was significantly correlated with gains of chromosomes III and X. Chromosome X disomy alone was sufficient to disrupt chromatin silencing and yeast mating-type identity as indicated by a lack of growth response to pheromone...
August 25, 2017: ELife
https://www.readbyqxmd.com/read/28840243/dna-sequences-in-centromere-formation-and-function
#13
M Dumont, D Fachinetti
Faithful chromosome segregation during cell division depends on the centromere, a complex DNA/protein structure that links chromosomes to spindle microtubules. This chromosomal domain has to be marked throughout cell division and its chromosomal localization preserved across cell generations. From fission yeast to human, centromeres are established on a series of repetitive DNA sequences and on specialized centromeric chromatin. This chromatin is enriched with the histone H3 variant, named CENP-A, that was demonstrated to be the epigenetic mark that maintains centromere identity and function indefinitely...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28837318/rapid-isolation-of-centromeres-from-scheffersomyces-stipitis
#14
Mingfeng Cao, Arun Somwarpet Seetharam, Andrew Josef Severin, Zengyi Shao
Centromeres (CENs) are the chromosomal regions promoting kinetochore formation for faithful chromosome segregation. In yeasts, CENs have been recognized as the essential elements for extra-chromosomal DNA stabilization. However, the epigeneticity of CENs makes their localization on individual chromosomes very challenging, especially in many not well-studied nonconventional yeast species. Previously, we applied a stepwise method to identify a 500-bp CEN5 from Scheffersomyces stipitis chromosome 5 and experimentally confirmed its critical role on improving plasmid stability...
September 5, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28809826/high-throughput-screening-for-protein-based-inheritance-in-s-cerevisiae
#15
James S Byers, Daniel F Jarosz
The encoding of biological information that is accessible to future generations is generally achieved via changes to the DNA sequence. Long-lived inheritance encoded in protein conformation (rather than sequence) has long been viewed as paradigm-shifting but rare. The best characterized examples of such epigenetic elements are prions, which possess a self-assembling behavior that can drive the heritable manifestation of new phenotypes. Many archetypal prions display a striking N/Q-rich sequence bias and assemble into an amyloid fold...
August 8, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28715382/odelay-a-large-scale-method-for-multi-parameter-quantification-of-yeast-growth
#16
Thurston Herricks, Fred D Mast, Song Li, John D Aitchison
Growth phenotypes of microorganisms are a strong indicator of their underlying genetic fitness and can be segregated into 3 growth regimes: lag-phase, log-phase, and stationary-phase. Each growth phase can reveal different aspects of fitness that are related to various environmental and genetic conditions. High-resolution and quantitative measurements of all 3 phases of growth are generally difficult to obtain. Here we present a detailed method to characterize all 3 growth phases on solid media using an assay called One-cell Doubling Evaluation of Living Arrays of Yeast (ODELAY)...
July 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28682306/unique-roles-for-histone-h3k9me-states-in-rnai-and-heritable-silencing-of-transcription
#17
Gloria Jih, Nahid Iglesias, Mark A Currie, Natarajan V Bhanu, Joao A Paulo, Steven P Gygi, Benjamin A Garcia, Danesh Moazed
Heterochromatic DNA domains have important roles in the regulation of gene expression and maintenance of genome stability by silencing repetitive DNA elements and transposons. From fission yeast to mammals, heterochromatin assembly at DNA repeats involves the activity of small noncoding RNAs (sRNAs) associated with the RNA interference (RNAi) pathway. Typically, sRNAs, originating from long noncoding RNAs, guide Argonaute-containing effector complexes to complementary nascent RNAs to initiate histone H3 lysine 9 di- and trimethylation (H3K9me2 and H3K9me3, respectively) and the formation of heterochromatin...
July 27, 2017: Nature
https://www.readbyqxmd.com/read/28665997/independent-regulation-of-gene-expression-level-and-noise-by-histone-modifications
#18
Shaohuan Wu, Ke Li, Yingshu Li, Tong Zhao, Ting Li, Yu-Fei Yang, Wenfeng Qian
The inherent stochasticity generates substantial gene expression variation among isogenic cells under identical conditions, which is frequently referred to as gene expression noise or cell-to-cell expression variability. Similar to (average) expression level, expression noise is also subject to natural selection. Yet it has been observed that noise is negatively correlated with expression level, which manifests as a potential constraint for simultaneous optimization of both. Here, we studied expression noise in human embryonic cells with computational analysis on single-cell RNA-seq data and in yeast with flow cytometry experiments...
June 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28619824/setd1b-encoding-a-histone-3-lysine-4-methyltransferase-is-a-maternal-effect-gene-required-for-the-oogenic-gene-expression-program
#19
David Brici, Qinyu Zhang, Susanne Reinhardt, Andreas Dahl, Hella Hartmann, Kerstin Schmidt, Neha Goveas, Jiahao Huang, Lenka Gahurova, Gavin Kelsey, Konstantinos Anastassiadis, A Francis Stewart, Andrea Kranz
Germ cell development involves major reprogramming of the epigenome to prime the zygote for totipotency. Histone 3 lysine 4 (H3K4) methylations are universal epigenetic marks mediated in mammals by six H3K4 methyltransferases related to fly Trithorax, including two yeast Set1 orthologs: Setd1a and Setd1b. Whereas Setd1a plays no role in oogenesis, we report that Setd1b deficiency causes female sterility in mice. Oocyte-specific Gdf9-iCre conditional knockout (Setd1b(Gdf9) cKO) ovaries develop through all stages; however, follicular loss accumulated with age and unfertilized metaphase II (MII) oocytes exhibited irregularities of the zona pellucida and meiotic spindle...
July 15, 2017: Development
https://www.readbyqxmd.com/read/28607149/polycomb-repressive-complex-2-in-an-autoinhibited-state
#20
COMPARATIVE STUDY
Matthew Bratkowski, Xin Yang, Xin Liu
Polycomb-group proteins control many fundamental biological processes, such as anatomical development in mammals and vernalization in plants. Polycomb repressive complex 2 (PRC2) is responsible for methylation of histone H3 lysine 27 (H3K27), and trimethylated H3K27 (H3K27me3) is implicated in epigenetic gene silencing. Recent genomic, biochemical, and structural data indicate that PRC2 is broadly conserved from yeast to human in many aspects. Here, we determined the crystal structure of an apo-PRC2 from the fungus Chaetomium thermophilum captured in a bona fide autoinhibited state, which represents a novel conformation of PRC2 associated with enzyme regulation in light of the basal and stimulated states that we reported previously...
August 11, 2017: Journal of Biological Chemistry
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