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Clr3 hdac

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https://www.readbyqxmd.com/read/27223649/unraveling-site-specific-and-combinatorial-histone-modifications-using-high-resolution-mass-spectrometry-in-histone-deacetylase-mutants-of-fission-yeast
#1
Nebiyu Abshiru, Roshan Elizabeth Rajan, Alain Verreault, Pierre Thibault
Histone deacetylases (HDACs) catalyze the removal of acetylation marks from lysine residues on histone and nonhistone substrates. Their activity is generally associated with essential cellular processes such as transcriptional repression and heterochromatin formation. Interestingly, abnormal activity of HDACs has been reported in various types of cancers, which makes them a promising therapeutic target for cancer treatment. In the current study, we aim to understand the mechanisms underlying the function of HDACs using an in-depth quantitative analysis of changes in histone acetylation levels in Schizosaccharomyces pombe (S...
July 1, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/26510788/escape-from-mitotic-arrest-an-unexpected-connection-between-microtubule-dynamics-and-epigenetic-regulation-of-centromeric-chromatin-in-schizosaccharomyces-pombe
#2
Anuja A George, Nancy C Walworth
Accurate chromosome segregation is necessary to ensure genomic integrity. Segregation depends on the proper functioning of the centromere, kinetochore, and mitotic spindle microtubules and is monitored by the spindle assembly checkpoint (SAC). In the fission yeast Schizosaccharomyces pombe, defects in Dis1, a microtubule-associated protein that influences microtubule dynamics, lead to mitotic arrest as a result of an active SAC and consequent failure to grow at low temperature. In a mutant dis1 background (dis1-288), loss of function of Msc1, a fission yeast homolog of the KDM5 family of proteins, suppresses the growth defect and promotes normal mitosis...
December 2015: Genetics
https://www.readbyqxmd.com/read/25487573/panspecies-small-molecule-disruptors-of-heterochromatin-mediated-transcriptional-gene-silencing
#3
Emilie Castonguay, Sharon A White, Alexander Kagansky, Daniel J St-Cyr, Araceli G Castillo, Christiane Brugger, Rachel White, Carolina Bonilla, Michaela Spitzer, William C Earnshaw, Thomas Schalch, Karl Ekwall, Mike Tyers, Robin C Allshire
Heterochromatin underpins gene repression, genome integrity, and chromosome segregation. In the fission yeast Schizosaccharomyces pombe, conserved protein complexes effect heterochromatin formation via RNA interference-mediated recruitment of a histone H3 lysine 9 methyltransferase to cognate chromatin regions. To identify small molecules that inhibit heterochromatin formation, we performed an in vivo screen for loss of silencing of a dominant selectable kanMX reporter gene embedded within fission yeast centromeric heterochromatin...
February 2015: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/24662054/the-mi-2-homolog-mit1-actively-positions-nucleosomes-within-heterochromatin-to-suppress-transcription
#4
Kevin M Creamer, Godwin Job, Sreenath Shanker, Geoffrey A Neale, Yuan-chi Lin, Blaine Bartholomew, Janet F Partridge
Mit1 is the putative chromatin remodeling subunit of the fission yeast Snf2/histone deacetylase (HDAC) repressor complex (SHREC) and is known to repress transcription at regions of heterochromatin. However, how Mit1 modifies chromatin to silence transcription is largely unknown. Here we report that Mit1 mobilizes histone octamers in vitro and requires ATP hydrolysis and conserved chromatin tethering domains, including a previously unrecognized chromodomain, to remodel nucleosomes and silence transcription. Loss of Mit1 remodeling activity results in nucleosome depletion at specific DNA sequences that display low intrinsic affinity for the histone octamer, but its contribution to antagonizing RNA polymerase II (Pol II) access and transcription is not restricted to these sites...
June 2014: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/23604080/hdac-mediated-suppression-of-histone-turnover-promotes-epigenetic-stability-of-heterochromatin
#5
Ozan Aygün, Sameet Mehta, Shiv I S Grewal
Heterochromatin causes epigenetic repression that can be transmitted through multiple cell divisions. However, the mechanisms underlying silencing and stability of heterochromatin are not fully understood. We show that heterochromatin differs from euchromatin in histone turnover and identify histone deacetylase (HDAC) Clr3 as a factor required for inhibiting histone turnover across heterochromatin domains in Schizosaccharomyces pombe. Loss of RNA-interference factors, Clr4 methyltransferase or HP1 proteins involved in HDAC localization causes increased histone turnover across pericentromeric domains...
May 2013: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/20876559/h2b-and-h3-specific-histone-deacetylases-are-required-for-dna-methylation-in-neurospora-crassa
#6
Kristina M Smith, Joseph R Dobosy, Jennifer E Reifsnyder, Michael R Rountree, D C Anderson, George R Green, Eric U Selker
Neurospora crassa utilizes DNA methylation to inhibit transcription of heterochromatin. DNA methylation is controlled by the histone methyltransferase DIM-5, which trimethylates histone H3 lysine 9, leading to recruitment of the DNA methyltransferase DIM-2. Previous work demonstrated that the histone deacetylase (HDAC) inhibitor trichostatin A caused a reduction in DNA methylation, suggesting involvement of histone deacetylation in DNA methylation. We therefore created mutants of each of the four classical N...
December 2010: Genetics
https://www.readbyqxmd.com/read/20081370/the-role-of-specific-hat-hdac-interactions-in-transcriptional-elongation
#7
Anna E Johnsson, Anthony P H Wright
We previously reported genome-wide evidence that the Gcn5 histone acetyltransferase (HAT) is located in the transcribed region of highly expressed genes and that it plays an important role in transcriptional elongation in the fission yeast, Schizosaccharomyces pombe (EMBO Reports 2009; 10:1009-14). Furthermore, the specific interplay between Gcn5 and the Clr3 histone deacetylase (HDAC) controls the acetylation levels of lysine-14 in histone H3 in the same class of highly expressed genes. Mutants of histone H3 that cannot be acetylated at residue 14 show similar stress phenotypes to those observed for mutants lacking Gcn5...
February 1, 2010: Cell Cycle
https://www.readbyqxmd.com/read/19633696/hat-hdac-interplay-modulates-global-histone-h3k14-acetylation-in-gene-coding-regions-during-stress
#8
Anna Johnsson, Mickaël Durand-Dubief, Yongtao Xue-Franzén, Michelle Rönnerblad, Karl Ekwall, Anthony Wright
Histone acetylation and deacetylation are important for gene regulation. The histone acetyltransferase, Gcn5, is an activator of transcriptional initiation that is recruited to gene promoters. Here, we map genome-wide Gcn5 occupancy and histone H3K14ac at high resolution. Gcn5 is predominantly localized to coding regions of highly transcribed genes, where it collaborates antagonistically with the class-II histone deacetylase, Clr3, to modulate H3K14ac levels and transcriptional elongation. An interplay between Gcn5 and Clr3 is crucial for the regulation of many stress-response genes...
September 2009: EMBO Reports
https://www.readbyqxmd.com/read/19443688/diverse-roles-of-hp1-proteins-in-heterochromatin-assembly-and-functions-in-fission-yeast
#9
Tamás Fischer, Bowen Cui, Jothy Dhakshnamoorthy, Ming Zhou, Chanan Rubin, Martin Zofall, Timothy D Veenstra, Shiv I S Grewal
Conserved chromosomal HP1 proteins capable of binding to histone H3 methylated at lysine 9 are believed to provide a dynamic platform for the recruitment and/or spreading of various regulatory proteins involved in diverse chromosomal processes. The fission yeast Schizosaccharomyces pombe HP1 family members Chp2 and Swi6 are important for heterochromatin assembly and transcriptional silencing, but their precise roles are not fully understood. Here, we show that Swi6 and Chp2 associate with histone deacetylase (HDAC) protein complexes containing class I HDAC Clr6 and class II HDAC Clr3 (a component of Snf2/HDAC repressor complex), which are critical for transcriptional silencing of centromeric repeats targeted by the heterochromatin machinery...
June 2, 2009: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/17101775/individual-subunits-of-the-ssn6-tup11-12-corepressor-are-selectively-required-for-repression-of-different-target-genes
#10
Fredrik Fagerström-Billai, Mikaël Durand-Dubief, Karl Ekwall, Anthony P H Wright
The Saccharomyces cerevisiae Ssn6 and Tup1 proteins form a corepressor complex that is recruited to target genes by DNA-bound repressor proteins. Repression occurs via several mechanisms, including interaction with hypoacetylated N termini of histones, recruitment of histone deacetylases (HDACs), and interactions with the RNA polymerase II holoenzyme. The distantly related fission yeast, Schizosaccharomyces pombe, has two partially redundant Tup1-like proteins that are dispensable during normal growth. In contrast, we show that Ssn6 is an essential protein in S...
February 2007: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/16246721/the-nucleation-and-maintenance-of-heterochromatin-by-a-histone-deacetylase-in-fission-yeast
#11
Takatomi Yamada, Wolfgang Fischle, Tomoyasu Sugiyama, C David Allis, Shiv I S Grewal
Posttranslational modifications of histones play an essential role in heterochromatin assembly. Whereas the role of Clr4/Suv39h-mediated methylation of histone H3 at lysine 9 (H3K9) in heterochromatin assembly is well studied, the exact function of histone deacetylases (HDACs) in this process is unclear. We show that Clr3, a fission yeast homolog of mammalian class II HDACs, acts in a distinct pathway parallel to RNAi-directed heterochromatin nucleation to recruit Clr4 and mediate H3K9 methylation at the silent mating-type region and centromeres...
October 28, 2005: Molecular Cell
https://www.readbyqxmd.com/read/16079916/genomewide-analysis-of-nucleosome-density-histone-acetylation-and-hdac-function-in-fission-yeast
#12
COMPARATIVE STUDY
Marianna Wirén, Rebecca A Silverstein, Indranil Sinha, Julian Walfridsson, Hang-Mao Lee, Patricia Laurenson, Lorraine Pillus, Daniel Robyr, Michael Grunstein, Karl Ekwall
We have conducted a genomewide investigation into the enzymatic specificity, expression profiles, and binding locations of four histone deacetylases (HDACs), representing the three different phylogenetic classes in fission yeast (Schizosaccharomyces pombe). By directly comparing nucleosome density, histone acetylation patterns and HDAC binding in both intergenic and coding regions with gene expression profiles, we found that Sir2 (class III) and Hos2 (class I) have a role in preventing histone loss; Clr6 (class I) is the principal enzyme in promoter-localized repression...
August 17, 2005: EMBO Journal
https://www.readbyqxmd.com/read/15289661/the-roles-of-histone-modifications-and-small-rna-in-centromere-function
#13
REVIEW
Karl Ekwall
Here, epigenetic regulation of centromeric chromatin in fission yeast (Schizosaccharomyces pombe) is reviewed, focussing on the role of histone modifications and the link to RNA interference (RNAi). Fission yeast centromeres are organized into two structurally and functionally distinct domains, both of which are required for centromere function. The central core domain anchors the kinetochore structure while the flanking heterochromatin domain is important for sister centromere cohesion. The chromatin structure of both domains is regulated epigenetically...
2004: Chromosome Research
https://www.readbyqxmd.com/read/11884604/functional-divergence-between-histone-deacetylases-in-fission-yeast-by-distinct-cellular-localization-and-in-vivo-specificity
#14
Pernilla Bjerling, Rebecca A Silverstein, Geneviève Thon, Amy Caudy, Shiv Grewal, Karl Ekwall
Histone deacetylases (HDACs) are important for gene regulation and the maintenance of heterochromatin in eukaryotes. Schizosaccharomyces pombe was used as a model system to investigate the functional divergence within this conserved enzyme family. S. pombe has three HDACs encoded by the hda1(+), clr3(+), and clr6(+) genes. Strains mutated in these genes have previously been shown to display strikingly different phenotypes when assayed for viability, chromosome loss, and silencing. Here, conserved differences in the substrate binding pocket identify Clr6 and Hda1 as class I HDACs, while Clr3 belongs in the class II family...
April 2002: Molecular and Cellular Biology
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