scholarly journals Yeast epigenetics: the inheritance of histone modification states

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Callum J. O’Kane ◽  
Edel M. Hyland
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Histone Modifications ◽  
Epigenetic Inheritance ◽  
S Phase ◽  
Model Systems ◽  
Nucleosome Dynamics ◽  
Current State ◽  
Higher Eukaryotes ◽  
First Time

Abstract Saccharomyces cerevisiae (budding yeast) and Schizosaccharomyces pombe (fission yeast) are two of the most recognised and well-studied model systems for epigenetic regulation and the inheritance of chromatin states. Their silent loci serve as a proxy for heterochromatic chromatin in higher eukaryotes, and as such both species have provided a wealth of information on the mechanisms behind the establishment and maintenance of epigenetic states, not only in yeast, but in higher eukaryotes. This review focuses specifically on the role of histone modifications in governing telomeric silencing in S. cerevisiae and centromeric silencing in S. pombe as examples of genetic loci that exemplify epigenetic inheritance. We discuss the recent advancements that for the first time provide a mechanistic understanding of how heterochromatin, dictated by histone modifications specifically, is preserved during S-phase. We also discuss the current state of our understanding of yeast nucleosome dynamics during DNA replication, an essential component in delineating the contribution of histone modifications to epigenetic inheritance.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Blend the Lab Course, Flip the Responsibility

2015 ◽  
pp. 1483-1505
Author(s):  
Mark A. Gallo
Keyword(s):  
Technical Problems ◽  
Student Responsibility ◽  
Class Time ◽  
Current State ◽  
Real Value ◽  
Upper Level ◽  
Intensive Course ◽  
First Time ◽  
Blended Course

An upper-level special topics course in Applied, Environmental, and Medical Microbiology was offered for the first time. It was decided by the author to offer it as a blended course. There were some compelling reasons to do so: first and foremost, it allowed class time to be spent doing what one should in a lab-intensive course: remark on current state of knowledge and literature, describe experimental design, discuss potential outcomes, troubleshoot technical problems as they arise, and offer suggestions regarding students' research throughout the process. The ultimate goal and real value of the blended classroom in this instance was elevating the level of student responsibility and forcing them to view a science class as something more than a collection of facts: rather as a very active class, one that requires individual action. It was also designed to allow the students to participate in fundamental scientific research with the help of a mentor in a manner that was/is still practiced and in full view of peer review. The role of the faculty member changes to one of providing guidance instead of content in the classroom, and so it gives one more individual time with the students; this time can be used for diagnostic, formative, and summative assessment.

scholarly journals Gastrointestinal symptoms in the course of COVID-19

2020 ◽  
Vol 74 ◽  
pp. 498-503
Author(s):  
Grzegorz K. Jakubiak ◽  
Józefina Ochab-Jakubiak ◽  
Grzegorz Cieślar ◽  
Agata Stanek
Keyword(s):  
Intestinal Inflammation ◽  
Gastrointestinal Symptoms ◽  
Unknown Etiology ◽  
Wuhan City ◽  
Angiotensin Converting Enzyme 2 ◽  
Current State ◽  
Novel Coronavirus ◽  
Loss Of Appetite ◽  
First Time

COVID-19 is an infectious disease caused by novel coronavirus SARS-CoV-2, a betacoronavirus comprised of single-stranded ribonucleic acid (RNA), the first time reported in December 2019 as pneumonia with unknown etiology in Wuhan City in China. It is a very important current problem for public health worldwide. A typical clinical course includes dyspnoea, dry cough and fever. In the presented paper we conducted the literature review and described the most important facts within the current state of knowledge about symptomatology and pathophysiology of gastrointestinal dysfunction in the course of COVID-19. Data about prevalence of gastrointestinal symptoms in the course of COVID-19 show wide divergence in the cited literature. Generally, the most common reported digestive symptoms were loss of appetite, nausea and vomiting. Liver injury in the course of COVID-19 is also an important and not well understood problem. The virus has high affinity to cells containing angiotensin- -converting enzyme 2 (ACE2) protein. Digestive symptoms of COVID-19 may be associated with ACE2 expression in epithelial cells in upper oesophagus, ileum and colon. Previous scientific reports have elucidated the role of ACE2 in modulating intestinal inflammation and diarrhoea.

scholarly journals Histone H3 lysine 56 acetylation by Rtt109 is crucial for chromosome positioning

2008 ◽  
Vol 183 (4) ◽  
pp. 641-651 ◽  
Author(s):  
Shin-ichiro Hiraga ◽  
Sotirios Botsios ◽  
Anne D. Donaldson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Replication ◽  
Histone Acetyltransferase ◽  
Nuclear Periphery ◽  
Histone H3 ◽  
Epigenetic Inheritance ◽  
S Phase ◽  
Chromosome Localization ◽  
Chromosome Domains ◽  
H3k56 Acetylation

Correct intranuclear organization of chromosomes is crucial for many genome functions, but the mechanisms that position chromatin are not well understood. We used a layered screen to identify Saccharomyces cerevisiae mutants defective in telomere localization to the nuclear periphery. We find that events in S phase are crucial for correct telomere localization. In particular, the histone chaperone Asf1 functions in telomere peripheral positioning. Asf1 stimulates acetylation of histone H3 lysine 56 (H3K56) by the histone acetyltransferase Rtt109. Analysis of rtt109Δ and H3K56 mutants suggests that the acetylation/deacetylation cycle of the H3K56 residue is required for proper telomere localization. The function of H3K56 acetylation in localizing chromosome domains is not confined to telomeres because deletion of RTT109 also prevents the correct peripheral localization of a newly identified S. cerevisiae “chromosome-organizing clamp” locus. Because chromosome positioning is subject to epigenetic inheritance, H3K56 acetylation may mediate correct chromosome localization by facilitating accurate transmission of chromatin status during DNA replication.

scholarly journals Cell Cycle Control of Cdc7p Kinase Activity through Regulation of Dbf4p Stability

1999 ◽  
Vol 19 (7) ◽  
pp. 4888-4896 ◽  
Author(s):  
Guy Oshiro ◽  
Julia C. Owens ◽  
Yiqun Shellman ◽  
Robert A. Sclafani ◽  
Joachim J. Li
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Dna Replication ◽  
Kinase Activity ◽  
Cell Cycle Control ◽  
S Phase ◽  
Regulatory Subunit ◽  
Anaphase Promoting Complex ◽  
Initiation Of Dna Replication

ABSTRACT In Saccharomyces cerevisiae, the heteromeric kinase complex Cdc7p-Dbf4p plays a pivotal role at replication origins in triggering the initiation of DNA replication during the S phase. We have assayed the kinase activity of endogenous levels of Cdc7p kinase by using a likely physiological target, Mcm2p, as a substrate. Using this assay, we have confirmed that Cdc7p kinase activity fluctuates during the cell cycle; it is low in the G1 phase, rises as cells enter the S phase, and remains high until cells complete mitosis. These changes in kinase activity cannot be accounted for by changes in the levels of the catalytic subunit Cdc7p, as these levels are constant during the cell cycle. However, the fluctuations in kinase activity do correlate with levels of the regulatory subunit Dbf4p. The regulation of Dbf4p levels can be attributed in part to increased degradation of the protein in G1 cells. This G1-phase instability is cdc16 dependent, suggesting a role of the anaphase-promoting complex in the turnover of Dbf4p. Overexpression of Dbf4p in the G1 phase can partially overcome this elevated turnover and lead to an increase in Cdc7p kinase activity. Thus, the regulation of Dbf4p levels through the control of Dbf4p degradation has an important role in the regulation of Cdc7p kinase activity during the cell cycle.

scholarly journals Genetic Analysis of the Shared Role of CLN3 and BCK2 at the G1-S Transition in Saccharomyces cerevisiae

Genetics ◽  
1999 ◽  
Vol 153 (3) ◽  
pp. 1131-1143
Author(s):  
Herman Wijnen ◽  
Bruce Futcher
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Analysis ◽  
Target Genes ◽  
S Phase ◽  
Negative Regulator ◽  
Growth Defect ◽  
Uncharacterized Protein ◽  
Number Of Genes ◽  
Transcription Complexes

Abstract The transcription complexes SBF and MBF mediate the G1-S transition in the cell cycle of Saccharomyces cerevisiae. In late G1, SBF and MBF induce a burst of transcription in a number of genes, including G1- and S-phase cyclins. Activation of SBF and MBF depends on the G1 cyclin Cln3 and a largely uncharacterized protein called Bck2. We show here that the induction of SBF/MBF target genes by Bck2 depends partly, but not wholly, on SBF and MBF. Unlike Cln3, Bck2 is capable of inducing its transcriptional targets in the absence of functional Cdc28. Our results revealed promoter-specific mechanisms of regulation by Cln3, Bck2, SBF, and MBF. We isolated high-copy suppressors of the cln3 bck2 growth defect; all of these had the ability to increase CLN2 expression. One of these suppressors was the negative regulator of meiosis RME1. Rme1 induces CLN2, and we show that it has a haploid-specific role in regulating cell size and pheromone sensitivity. Genetic analysis of the cln3 bck2 defect showed that CLN1, CLN2, and other SBF/MBF target genes have an essential role in addition to the degradation of Sic1.

scholarly journals The Role of the Rad55–Rad57 Complex in DNA Repair

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1390
Author(s):  
Upasana Roy ◽  
Eric C. Greene
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Repair ◽  
Homologous Recombination ◽  
Single Molecule ◽  
Genome Integrity ◽  
Genetic Studies ◽  
Biochemical Assays ◽  
Rad51 Paralogs ◽  
Higher Eukaryotes

Homologous recombination (HR) is a mechanism conserved from bacteria to humans essential for the accurate repair of DNA double-stranded breaks, and maintenance of genome integrity. In eukaryotes, the key DNA transactions in HR are catalyzed by the Rad51 recombinase, assisted by a host of regulatory factors including mediators such as Rad52 and Rad51 paralogs. Rad51 paralogs play a crucial role in regulating proper levels of HR, and mutations in the human counterparts have been associated with diseases such as cancer and Fanconi Anemia. In this review, we focus on the Saccharomyces cerevisiae Rad51 paralog complex Rad55–Rad57, which has served as a model for understanding the conserved role of Rad51 paralogs in higher eukaryotes. Here, we discuss the results from early genetic studies, biochemical assays, and new single-molecule observations that have together contributed to our current understanding of the molecular role of Rad55–Rad57 in HR.

scholarly journals S-phase-independent silencing establishment in Saccharomyces cerevisiae

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Davis Goodnight ◽  
Jasper Rine
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Histone Modifications ◽  
Single Molecule ◽  
Chromatin Immunoprecipitation ◽  
S Phase ◽  
Cell Cycles ◽  
Identical Cell ◽  
Protein Recruitment ◽  
Molecular Nature

The establishment of silent chromatin, a heterochromatin-like structure at HML and HMR in Saccharomyces cerevisiae, depends on progression through S phase of the cell cycle, but the molecular nature of this requirement has remained elusive despite intensive study. Using high-resolution chromatin immunoprecipitation and single-molecule RNA analysis, we found that silencing establishment proceeded via gradual repression of transcription in individual cells over several cell cycles, and that the cell-cycle-regulated step was downstream of Sir protein recruitment. In contrast to prior results, HML and HMR had identical cell-cycle requirements for silencing establishment, with no apparent contribution from a tRNA gene adjacent to HMR. We identified the cause of the S-phase requirement for silencing establishment: removal of transcription-favoring histone modifications deposited by Dot1, Sas2, and Rtt109. These results revealed that silencing establishment was absolutely dependent on the cell-cycle-regulated interplay between euchromatic and heterochromatic histone modifications.

scholarly journals Role for Upf2p Phosphorylation in Saccharomyces cerevisiae Nonsense-Mediated mRNA Decay

2006 ◽  
Vol 26 (9) ◽  
pp. 3390-3400 ◽  
Author(s):  
Weirong Wang ◽  
Iván J. Cajigas ◽  
Stuart W. Peltz ◽  
Miles F. Wilkinson ◽  
Carlos I. González
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mrna Decay ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Nonsense Mediated Mrna Decay ◽  
Higher Eukaryotes ◽  
Nonsense Codons ◽  
First Time

ABSTRACT Premature termination (nonsense) codons trigger rapid mRNA decay by the nonsense-mediated mRNA decay (NMD) pathway. Two conserved proteins essential for NMD, UPF1 and UPF2, are phosphorylated in higher eukaryotes. The phosphorylation and dephosphorylation of UPF1 appear to be crucial for NMD, as blockade of either event in Caenorhabditis elegans and mammals largely prevents NMD. The universality of this phosphorylation/dephosphorylation cycle pathway has been questioned, however, because the well-studied Saccharomyces cerevisiae NMD pathway has not been shown to be regulated by phosphorylation. Here, we used in vitro and in vivo biochemical techniques to show that both S. cerevisiae Upf1p and Upf2p are phosphoproteins. We provide evidence that the phosphorylation of the N-terminal region of Upf2p is crucial for its interaction with Hrp1p, an RNA-binding protein that we previously showed is essential for NMD. We identify specific amino acids in Upf2p's N-terminal domain, including phosphorylated serines, which dictate both its interaction with Hrp1p and its ability to elicit NMD. Our results indicate that phosphorylation of UPF1 and UPF2 is a conserved event in eukaryotes and for the first time provide evidence that Upf2p phosphorylation is crucial for NMD.

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