scholarly journals Subtelomeric Chromatin in the Fission Yeast S. pombe

2021 ◽  
Vol 9 (9) ◽  
pp. 1977
Author(s):  
Rajesh K. Yadav ◽  
Atsushi Matsuda ◽  
Brandon R. Lowe ◽  
Yasushi Hiraoka ◽  
Janet F. Partridge
Keyword(s):  
Fission Yeast ◽  
Constitutive Heterochromatin ◽  
Genetic Manipulation ◽  
Protective Role ◽  
Regulatory Proteins ◽  
H3k36 Methylation ◽  
Chromatin Regulators ◽  
Repetitive Nature ◽  
Associated Sequences ◽  
Chromatin Biology

Telomeres play important roles in safeguarding the genome. The specialized repressive chromatin that assembles at telomeres and subtelomeric domains is key to this protective role. However, in many organisms, the repetitive nature of telomeric and subtelomeric sequences has hindered research efforts. The fission yeast S. pombe has provided an important model system for dissection of chromatin biology due to the relative ease of genetic manipulation and strong conservation of important regulatory proteins with higher eukaryotes. Telomeres and the telomere-binding shelterin complex are highly conserved with mammals, as is the assembly of constitutive heterochromatin at subtelomeres. In this review, we seek to summarize recent work detailing the assembly of distinct chromatin structures within subtelomeric domains in fission yeast. These include the heterochromatic SH subtelomeric domains, the telomere-associated sequences (TAS), and ST chromatin domains that assemble highly condensed chromatin clusters called knobs. Specifically, we review new insights into the sequence of subtelomeric domains, the distinct types of chromatin that assemble on these sequences and how histone H3 K36 modifications influence these chromatin structures. We address the interplay between the subdomains of chromatin structure and how subtelomeric chromatin is influenced by both the telomere-bound shelterin complexes and by euchromatic chromatin regulators internal to the subtelomeric domain. Finally, we demonstrate that telomere clustering, which is mediated via the condensed ST chromatin knob domains, does not depend on knob assembly within these domains but on Set2, which mediates H3K36 methylation.

scholarly journals SUV39 SET domains mediate crosstalk of heterochromatic histone marks

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Alessandro Stirpe ◽  
Nora Guidotti ◽  
Sarah J Northall ◽  
Sinan Kilic ◽  
Alexandre Hainard ◽  
...  
Keyword(s):  
Structure Function ◽  
Fission Yeast ◽  
Catalytic Domain ◽  
Constitutive Heterochromatin ◽  
Histone H3 ◽  
H3k9 Methylation ◽  
Set Domain ◽  
Heterochromatin Formation ◽  
Heterochromatin Silencing ◽  
Genomic Regions

The SUV39 class of methyltransferase enzymes deposits histone H3 lysine 9 di- and trimethylation (H3K9me2/3), the hallmark of constitutive heterochromatin. How these enzymes are regulated to mark specific genomic regions as heterochromatic is poorly understood. Clr4 is the sole H3K9me2/3 methyltransferase in the fission yeast Schizosaccharomyces pombe, and recent evidence suggests that ubiquitination of lysine 14 on histone H3 (H3K14ub) plays a key role in H3K9 methylation. However, the molecular mechanism of this regulation and its role in heterochromatin formation remain to be determined. Our structure-function approach shows that the H3K14ub substrate binds specifically and tightly to the catalytic domain of Clr4, and thereby stimulates the enzyme by over 250-fold. Mutations that disrupt this mechanism lead to a loss of H3K9me2/3 and abolish heterochromatin silencing similar to clr4 deletion. Comparison with mammalian SET domain proteins suggests that the Clr4 SET domain harbors a conserved sensor for H3K14ub, which mediates licensing of heterochromatin formation.

scholarly journals Phosphorylation of repressive histone code readers by casein kinase 2 plays diverse roles in heterochromatin regulation

2019 ◽  
Vol 166 (1) ◽  
pp. 3-6 ◽  
Author(s):  
Yota Murakami
Keyword(s):  
Histone Modifications ◽  
Constitutive Heterochromatin ◽  
Histone H3 ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Histone Code ◽  
Effector Proteins ◽  
Regulatory Proteins ◽  
Silent Chromatin ◽  
Facultative Heterochromatin

Abstract Heterochromatin is a condensed and transcriptionally silent chromatin structure and that plays important roles in epigenetic regulation of the genome. Two types of heterochromatin exist: constitutive heterochromatin is primarily associated with trimethylation of histone H3 at lysine 9 (H3K9me3), and facultative heterochromatin with trimethylation of H3 at lysine 27 (H3K27me3). The methylated histones are bound by the chromodomain of histone code ‘reader’ proteins: HP1 family proteins for H3K9me3 and Polycomb family proteins for H3K27me3. Each repressive reader associates with various ‘effector’ proteins that provide the functional basis of heterochromatin. Heterochromatin regulation is primarily achieved by controlling histone modifications. However, recent studies have revealed that the repressive readers are phosphorylated, like other regulatory proteins, suggesting that phosphorylation also participates in heterochromatin regulation. Detailed studies have shown that phosphorylation of readers affects the binding specificities of chromodomains for methylated histone H3, as well as the binding of effector proteins. Thus, phosphorylation adds another layer to heterochromatin regulation. Interestingly, casein kinase 2, a strong and predominant kinase within the cell, is responsible for phosphorylation of repressive readers. In this commentary, I summarize the regulation of repressive readers by casein kinase 2-dependent phosphorylation and discuss the functional meaning of this modification.

scholarly journals Structural Genomics of Chromatin Regulators for Biological Discovery & Epigenetic Therapy

2014 ◽  
Vol 70 (a1) ◽  
pp. C33-C33
Author(s):  
Cheryl Arrowsmith
Keyword(s):  
Posttranslational Modifications ◽  
Regulatory Proteins ◽  
Epigenetic Therapy ◽  
Histone Tail ◽  
Nuclear Signaling ◽  
Chromatin Regulators ◽  
Family Approach ◽  
Biological Discovery ◽  
Key Features ◽  
Biochemical Analyses

We are taking a protein family approach to understand how human protein domains, enzymes and complexes recognize specific histone tail sequences and their posttranslational modifications. These are key mechanisms of nuclear signaling that regulate epigenetic cellular states and gene expression programs. Systematic structural and biochemical analyses are revealing key features of selectivity and regulation among these factors, enabling structure-based development of potent, selective, cell-active small molecule inhibitors of individual epigenetic regulatory proteins.

scholarly journals The dual role of fission yeast Tbc1/cofactor C orchestrates microtubule homeostasis in tubulin folding and acts as a GAP for GTPase Alp41/Arl2

2013 ◽  
Vol 24 (11) ◽  
pp. 1713-1724 ◽  
Author(s):  
Risa Mori ◽  
Takashi Toda
Keyword(s):  
Fission Yeast ◽  
Molecular Level ◽  
Dual Role ◽  
Small Gtpase ◽  
Microtubule Dynamics ◽  
Regulatory Proteins ◽  
Dependent Manner ◽  
Continuous Cycling ◽  
Β Tubulin

Supplying the appropriate amount of correctly folded α/β-tubulin heterodimers is critical for microtubule dynamics. Formation of assembly-competent heterodimers is remarkably elaborate at the molecular level, in which the α- and β-tubulins are separately processed in a chaperone-dependent manner. This sequential step is performed by the tubulin-folding cofactor pathway, comprising a specific set of regulatory proteins: cofactors A–E. We identified the fission yeast cofactor: the orthologue of cofactor C, Tbc1. In addition to its roles in tubulin folding, Tbc1 acts as a GAP in regulating Alp41/Arl2, a highly conserved small GTPase. Of interest, the expression of GDP- or GTP-bound Alp41 showed the identical microtubule loss phenotype, suggesting that continuous cycling between these forms is important for its functions. In addition, we found that Alp41 interacts with Alp1D, the orthologue of cofactor D, specifically when in the GDP-bound form. Intriguingly, Alp1D colocalizes with microtubules when in excess, eventually leading to depolymerization, which is sequestered by co-overproducing GDP-bound Alp41. We present a model of the final stages of the tubulin cofactor pathway that includes a dual role for both Tbc1 and Alp1D in opposing regulation of the microtubule.

scholarly journals Distinct Regulatory Proteins Control the Graded Transcriptional Response to Increasing H2O2 Levels in Fission Yeast Schizosaccharomyces pombe

2002 ◽  
Vol 13 (3) ◽  
pp. 805-816 ◽  
Author(s):  
Janet Quinn ◽  
Victoria J. Findlay ◽  
Keren Dawson ◽  
Jonathan B.A. Millar ◽  
Nic Jones ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Protein Kinase ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Transcriptional Response ◽  
Regulatory Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Two Component ◽  
Mitogen Activated Protein ◽  
Low Levels

The signaling pathways that sense adverse stimuli and communicate with the nucleus to initiate appropriate changes in gene expression are central to the cellular stress response. Herein, we have characterized the role of the Sty1 (Spc1) stress-activated mitogen-activated protein kinase pathway, and the Pap1 and Atf1 transcription factors, in regulating the response to H2O2 in the fission yeast Schizosaccharomyces pombe. We find that H2O2 activates the Sty1 pathway in a dose-dependent manner via at least two sensing mechanisms. At relatively low levels of H2O2, a two component-signaling pathway, which feeds into either of the two stress-activated mitogen-activated protein kinase kinase kinases Wak1 or Win1, regulates Sty1 phosphorylation. In contrast, at high levels of H2O2, Sty1 activation is controlled predominantly by a two-component independent mechanism and requires the function of both Wak1 and Win1. Individual transcription factors were also found to function within a limited range of H2O2 concentrations. Pap1 activates target genes primarily in response to low levels of H2O2, whereas Atf1 primarily controls the transcriptional response to high concentrations of H2O2. Our results demonstrate that S. pombe uses a combination of stress-responsive regulatory proteins to gauge and effect the appropriate transcriptional response to increasing concentrations of H2O2.

scholarly journals Biology and physics of heterochromatin-like domains/complexes

2020 ◽  
Author(s):  
Prim B. Singh ◽  
Stepan N. Belyakin ◽  
Petr P. Laktionov
Keyword(s):  
Phase Separation ◽  
Fission Yeast ◽  
Constitutive Heterochromatin ◽  
Thermodynamic Description ◽  
Dynamic Structure ◽  
Vertebrate Development ◽  
Type Region ◽  
Additional Tool ◽  
3D Genome ◽  
Yeast Regulation

AbstractThe hallmarks of constitutive heterochromatin, HP1 and H3K9me2/3, assemble heterochromatin-like domains/complexes outside canonical constitutively heterochromatic territories where they regulate chromatin-templated processes. Domains are more than 100kb in size; complexes less than 100kb. They are present in the genomes of organisms ranging from fission yeast to man, with an expansion in size and number in mammals. Some of the likely functions of the domains/complexes include silencing of the donor mating type region in fission yeast, regulation of mammalian imprinted genes and the phylotypic progression during vertebrate development. Far cis- and trans-contacts between micro-phase separated domains/complexes in mammalian nuclei contribute to the emergence of epigenetic compartmental domains (ECDs) detected in Hi-C maps. We speculate that a thermodynamic description of micro-phase separation of heterochromatin-like domains/complexes will require a gestalt shift away from the monomer as the “unit of incompatibility”, where it is the choice of monomer that determines the sign and magnitude of the Flory-Huggins parameter, χ. Instead, a more dynamic structure, the oligo-nucleosomal “clutch”, consisting of between 2 to 10 nucleosomes is both the long sought-after secondary structure of chromatin and its unit of incompatibility. Based on this assumption we present a simple theoretical framework that enables an estimation of χ for domains/complexes flanked by euchromatin and thereby an indication of their tendency to phase separate. The degree of phase separation is specified by χN, where N is the number of “clutches” in a domain/complex. Our approach may provide an additional tool for understanding the biophysics of the 3D genome.

scholarly journals Disrupting HIV-1 capsid formation causes cGAS sensing of viral DNA

2019 ◽  
Author(s):  
Rebecca P. Sumner ◽  
Lauren Harrison ◽  
Emma Touizer ◽  
Thomas P. Peacock ◽  
Matthew Spencer ◽  
...  
Keyword(s):  
Genetic Manipulation ◽  
Protective Role ◽  
Type I ◽  
Viral Dna ◽  
Innate And Adaptive Immunity ◽  
Capsid Formation ◽  
Diminished Capacity ◽  
Viral Particles ◽  
Hiv 1

SummaryDetection of viral DNA by cyclic GMP-AMP synthase (cGAS) is a first line of defence leading to the production of type-I interferon (IFN). As HIV-1 is not a strong inducer of IFN we have hypothesised that its capsid cloaks viral DNA from cGAS. To test this we generated defective viral particles by treatment with HIV-1 protease inhibitors or by genetic manipulation of gag. These viruses had defective Gag cleavage, reduced infectivity and diminished capacity to saturate TRIM5α. Importantly, unlike wild-type HIV-1, infection with cleavage defective HIV-1 triggered an IFN response in THP-1 cells and primary human macrophages that was dependent on viral DNA and cGAS. Infection in the presence of the capsid destabilising small molecule PF-74 also induced a cGAS-dependent IFN response. These data demonstrate a protective role for capsid and suggest that antiviral activity of capsid- and protease-targeting antivirals may benefit from enhanced innate and adaptive immunity in vivo.

scholarly journals Generation and characterisation of temperature sensitive mutants of genes encoding the fission yeast spindle pole body

2017 ◽  
Author(s):  
Ngang Heok Tang ◽  
Chii Shyang Fong ◽  
Hirohisa Masuda ◽  
Isabelle Jourdain ◽  
Masashi Yukawa ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Genetic Manipulation ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Temperature Sensitive ◽  
Cellular Processes ◽  
Temperature Sensitive Mutants ◽  
Pole Body ◽  
Genes Encoding ◽  
Mitosis And Meiosis

The spindle pole body (SPB) in fungi is the equivalent of the animal centrosome. A number of previous studies have identified many, if not all, components of the SPB. The SPB is the structural platform for microtubule nucleation and plays important roles, both in mitosis and meiosis. The SPB is absolutely essential for cell survival and its abnormalities give rise to aberrant cell division and morphogenesis. Therefore, it is crucial to understand how the SPB organises itself and how the functions of individual SPB components are regulated. We report here a procedure to generate temperature sensitive mutants in the fission yeast, Schizosaccharomyces pombe. The approach has proved useful to characterise functions of individual SPB components. This original genetic manipulation is however not restricted to analysis of SPB functions, and can be suited to investigate other cellular processes in S. pombe.

scholarly journals Nuclear size control in fission yeast

2007 ◽  
Vol 179 (4) ◽  
pp. 593-600 ◽  
Author(s):  
Frank R. Neumann ◽  
Paul Nurse
Keyword(s):  
Fission Yeast ◽  
Cell Size ◽  
Nuclear Dna ◽  
Genetic Manipulation ◽  
Relative Size ◽  
Nuclear Dna Content ◽  
Size Control ◽  
Volume Ratio ◽  
Nuclear Size ◽  
Rapid Expansion

A long-standing biological question is how a eukaryotic cell controls the size of its nucleus. We report here that in fission yeast, nuclear size is proportional to cell size over a 35-fold range, and use mutants to show that a 16-fold change in nuclear DNA content does not influence the relative size of the nucleus. Multi-nucleated cells with unevenly distributed nuclei reveal that nuclei surrounded by a greater volume of cytoplasm grow more rapidly. During interphase of the cell cycle nuclear growth is proportional to cell growth, and during mitosis there is a rapid expansion of the nuclear envelope. When the nuclear/cell (N/C) volume ratio is increased by centrifugation or genetic manipulation, nuclear growth is arrested while the cell continues to grow; in contrast, low N/C ratios are rapidly corrected by nuclear growth. We propose that there is a general cellular control linking nuclear growth to cell size.

scholarly journals Identification of two telomere-proximal fission yeast DNA replication origins constrained by nearby cis-acting sequences to replicate in late S phase

F1000Research ◽  
2012 ◽  
Vol 1 ◽  
pp. 58 ◽  
Author(s):  
Amna Chaudari ◽  
Joel A Huberman
Keyword(s):  
Dna Replication ◽  
Fission Yeast ◽  
S Phase ◽  
Yeast Genome ◽  
Late Replication ◽  
Replication Origins ◽  
Replication Checkpoint ◽  
Cis Acting ◽  
Associated Sequences ◽  
Dna Replication Origins

Telomeres of the fission yeast, Schizosaccharomyces pombe, are known to replicate in late S phase, but the reasons for this late replication are not fully understood. We have identified two closely-spaced DNA replication origins, 5.5 to 8 kb upstream from the telomere itself. These are the most telomere-proximal of all the replication origins in the fission yeast genome. When located by themselves in circular plasmids, these origins fired in early S phase, but if flanking sequences closer to the telomere were included in the circular plasmid, then replication was restrained to late S phase – except in cells lacking the replication-checkpoint kinase, Cds1. We conclude that checkpoint-dependent late replication of telomere-associated sequences is dependent on nearby cis-acting sequences, not on proximity to the physical end of a linear chromosome.

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