scholarly journals The N-Terminal Tail of Histone H3 Regulates Copper Homeostasis in Saccharomyces cerevisiae

2020 ◽  
Author(s):  
Sakshi Singh ◽  
Rakesh Kumar Sahu ◽  
Raghuvir Singh Tomar
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Regulation ◽  
Transcriptional Regulation ◽  
Histone H3 ◽  
Copper Homeostasis ◽  
Tata Binding Protein ◽  
Copper Stress ◽  
Toxic Level ◽  
Cellular Processes

Copper homeostasis is crucial for cellular processes. The balance between nutritional and toxic level is maintained through the regulation of uptake, distribution and detoxification via antagonistic actions of two transcription factors AceI and Mac1. AceI responds to toxic copper levels by transcriptional regulation of detoxification genes CUP1 and CRS5. Cup1 metallothionein (MT) confers protection against toxic copper levels. CUP1 gene regulation is a multifactorial event requiring AceI, TBP (TATA-binding protein), chromatin remodeler, acetyltransferase (Spt10) and histones. However, the role of histone H3 residues has not been fully elucidated. To investigate the role of H3 tail in CUP1 transcriptional regulation, we screened the library of histone mutants in copper stress. We identified mutations in H3 (K23Q, K27R, K36Q, Δ5-16, Δ13-16, Δ13-28, Δ25-28, Δ28-31, Δ29-32) that reduce CUP1 expression. We detected reduced AceI occupancy across CUP1 promoter in K23Q, K36Q, Δ5-16, Δ13-28, Δ25-28 and Δ28-31 correlating with the reduced CUP1 transcription. Majority of these mutations affect TBP occupancy at CUP1 promoter augmenting the CUP1 transcription defect. Additionally, some mutants display cytosolic protein aggregation upon copper stress. Altogether, our data establish previously unidentified residues of H3 N-terminal tail and their modifications in CUP1 regulation.

Analysis of Saccharomyces cerevisiae histone H3 mutants reveals the role of the αN helix in nucleosome function

2008 ◽  
Vol 374 (3) ◽  
pp. 543-548 ◽  
Author(s):  
Ja-Hwan Seol ◽  
Hye-Jin Kim ◽  
Ja-Kyung Yoo ◽  
Hyun-Ju Park ◽  
Eun-Jung Cho
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Histone H3

scholarly journals Unique Role of Caffeine Compared to Other Methylxanthines (Theobromine, Theophylline, Pentoxifylline, Propentofylline) in Regulation of AD Relevant Genes in Neuroblastoma SH-SY5Y Wild Type Cells

2020 ◽  
Vol 21 (23) ◽  
pp. 9015
Author(s):  
Daniel Janitschke ◽  
Anna A. Lauer ◽  
Cornel M. Bachmann ◽  
Martin Seyfried ◽  
Heike S. Grimm ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Transcriptional Regulation ◽  
Expression Patterns ◽  
Wild Type ◽  
Neuronal Function ◽  
Purine Base ◽  
Unique Role ◽  
Beneficial Effects ◽  
Other Substances

Methylxanthines are a group of substances derived from the purine base xanthine with a methyl group at the nitrogen on position 3 and different residues at the nitrogen on position 1 and 7. They are widely consumed in nutrition and used as pharmaceuticals. Here we investigate the transcriptional regulation of 83 genes linked to Alzheimer’s disease in the presence of five methylxanthines, including the most prominent naturally occurring methylxanthines—caffeine, theophylline and theobromine—and the synthetic methylxanthines pentoxifylline and propentofylline. Methylxanthine-regulated genes were found in pathways involved in processes including oxidative stress, lipid homeostasis, signal transduction, transcriptional regulation, as well as pathways involved in neuronal function. Interestingly, multivariate analysis revealed different or inverse effects on gene regulation for caffeine compared to the other methylxanthines, which was further substantiated by multiple comparison analysis, pointing out a distinct role for caffeine in gene regulation. Our results not only underline the beneficial effects of methylxanthines in the regulation of genes in neuroblastoma wild-type cells linked to neurodegenerative diseases in general, but also demonstrate that individual methylxanthines like caffeine mediate unique or inverse expression patterns. This suggests that the replacement of single methylxanthines by others could result in unexpected effects, which could not be anticipated by the comparison to other substances in this substance class.

scholarly journals Insights into the Role of Histone H3 and Histone H4 Core Modifiable Residues in Saccharomyces cerevisiae

2005 ◽  
Vol 25 (24) ◽  
pp. 11193-11193 ◽  
Author(s):  
Edel M. Hyland ◽  
Michael S. Cosgrove ◽  
Henrik Molina ◽  
Dongxia Wang ◽  
Akhilesh Pandey ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Histone H3 ◽  
Histone H4

scholarly journals The Saccharomyces cerevisiae SPT8 gene encodes a very acidic protein that is functionally related to SPT3 and TATA-binding protein.

Genetics ◽  
1994 ◽  
Vol 137 (3) ◽  
pp. 647-657 ◽  
Author(s):  
D M Eisenmann ◽  
C Chapon ◽  
S M Roberts ◽  
C Dollard ◽  
F Winston
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Binding Protein ◽  
Tata Binding Protein ◽  
Sequence Motif ◽  
Heterotrimeric G Proteins ◽  
Eukaryotic Proteins ◽  
Multiple Copies ◽  
The Relationship ◽  
Insertion Mutations

Abstract Mutations in the Saccharomyces cerevisiae SPT8 gene were previously isolated as suppressors of retrotransposon insertion mutations in the 5' regions of the HIS4 and LYS2 genes. Mutations in SPT8 confer phenotypes similar to those caused by particular mutations in SPT15, which encodes the TATA-binding protein (TBP). These phenotypes are also similar to those caused by mutations in the SPT3 gene, which encodes a protein that directly interacts with TBP. We have now cloned and sequenced the SPT8 gene and have shown that it encodes a predicted protein of 602 amino acids with an extremely acidic amino terminus. In addition, the predicted SPT8 amino acid sequence contains one copy of a sequence motif found in multiple copies in a number of other eukaryotic proteins, including the beta subunit of heterotrimeric G proteins. To investigate further the relationship between SPT8, SPT3 and TBP, we have analyzed the effect of an spt8 null mutation in combination with different spt3 and spt15 mutations. This genetic analysis has shown that an spt8 deletion mutation is suppressed by particular spt3 alleles. Taken together with previous results, these data suggest that the SPT8 protein is required, directly or indirectly, for TBP function at particular promoters and that the role of SPT8 may be to promote a functional interaction between SPT3 and TBP.

scholarly journals H2B Ubiquitin Protease Ubp8 and Sgf11 Constitute a Discrete Functional Module within the Saccharomyces cerevisiae SAGA Complex

2005 ◽  
Vol 25 (3) ◽  
pp. 1162-1172 ◽  
Author(s):  
Kristin Ingvarsdottir ◽  
Nevan J. Krogan ◽  
N. C. Tolga Emre ◽  
Anastasia Wyce ◽  
Natalie J. Thompson ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Regulation ◽  
Transcriptional Activation ◽  
Functional Module ◽  
Gene Activation ◽  
Tata Binding Protein ◽  
Binding Domain ◽  
Genetic Interactions ◽  
Saga Complex ◽  
Microarray Analyses

ABSTRACT The SAGA complex is a multisubunit protein complex involved in transcriptional regulation in Saccharomyces cerevisiae. SAGA combines proteins involved in interactions with DNA-bound activators and TATA-binding protein (TBP), as well as enzymes for histone acetylation (Gcn5) and histone deubiquitylation (Ubp8). We recently showed that H2B ubiquitylation and Ubp8-mediated deubiquitylation are both required for transcriptional activation. For this study, we investigated the interaction of Ubp8 with SAGA. Using mutagenesis, we identified a putative zinc (Zn) binding domain within Ubp8 as being critical for the association with SAGA. The Zn binding domain is required for H2B deubiquitylation and for growth on media requiring Ubp8's function in gene activation. Furthermore, we identified an 11-kDa subunit of SAGA, Sgf11, and showed that it is required for the Ubp8 association with SAGA and for H2B deubiquitylation. Different approaches indicated that the functions of Ubp8 and Sgf11 are related and separable from those of other components of SAGA. In particular, the profiles of Ubp8 and Sgf11 deletions were remarkably similar in microarray analyses and synthetic genetic interactions and were distinct from those of the Spt3 and Spt8 subunits of SAGA, which are involved in TBP regulation. These data indicate that Ubp8 and Sgf11 likely represent a new functional module within SAGA that is involved in gene regulation through H2B deubiquitylation.

scholarly journals A novel role for Dun1 in the regulation of origin firing upon hyper-acetylation of H3K56

PLoS Genetics ◽  
2021 ◽  
Vol 17 (2) ◽  
pp. e1009391
Author(s):  
Lihi Gershon ◽  
Martin Kupiec
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Histone Deacetylases ◽  
Large Subunit ◽  
Histone H3 ◽  
Clamp Loader ◽  
Origin Firing ◽  
Sister Chromatids ◽  
Leading Strand

During DNA replication newly synthesized histones are incorporated into the chromatin of the replicating sister chromatids. In the yeast Saccharomyces cerevisiae new histone H3 molecules are acetylated at lysine 56. This modification is carefully regulated during the cell cycle, and any disruption of this process is a source of genomic instability. Here we show that the protein kinase Dun1 is necessary in order to maintain viability in the absence of the histone deacetylases Hst3 and Hst4, which remove the acetyl moiety from histone H3. This lethality is not due to the well-characterized role of Dun1 in upregulating dNTPs, but rather because Dun1 is needed in order to counteract the checkpoint kinase Rad53 (human CHK2) that represses the activity of late firing origins. Deletion of CTF18, encoding the large subunit of an alternative RFC-like complex (RLC), but not of components of the Elg1 or Rad24 RLCs, is enough to overcome the dependency of cells with hyper-acetylated histones on Dun1. We show that the detrimental function of Ctf18 depends on its interaction with the leading strand polymerase, Polε. Our results thus show that the main problem of cells with hyper-acetylated histones is the regulation of their temporal and replication programs, and uncover novel functions for the Dun1 protein kinase and the Ctf18 clamp loader.

scholarly journals The role of SUMOylation during development

2020 ◽  
Vol 48 (2) ◽  
pp. 463-478
Author(s):  
Ana Talamillo ◽  
Orhi Barroso-Gomila ◽  
Immacolata Giordano ◽  
Leiore Ajuria ◽  
Marco Grillo ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Cell Cycle Progression ◽  
Nucleocytoplasmic Transport ◽  
Chromatin Remodelers ◽  
Cellular Processes ◽  
Chromatin Regulators ◽  
Multicellular Organisms ◽  
Dna Maintenance ◽  
Translational Process

During the development of multicellular organisms, transcriptional regulation plays an important role in the control of cell growth, differentiation and morphogenesis. SUMOylation is a reversible post-translational process involved in transcriptional regulation through the modification of transcription factors and through chromatin remodelling (either modifying chromatin remodelers or acting as a ‘molecular glue’ by promoting recruitment of chromatin regulators). SUMO modification results in changes in the activity, stability, interactions or localization of its substrates, which affects cellular processes such as cell cycle progression, DNA maintenance and repair or nucleocytoplasmic transport. This review focuses on the role of SUMO machinery and the modification of target proteins during embryonic development and organogenesis of animals, from invertebrates to mammals.

scholarly journals Enhanced scale and scope of genome engineering and regulation using CRISPR/Cas in Saccharomyces cerevisiae

2019 ◽  
Vol 19 (7) ◽  
Author(s):  
Matthew Deaner ◽  
Hal S Alper
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Regulation ◽  
Transcriptional Regulation ◽  
Gene Editing ◽  
Genome Engineering ◽  
Guide Rna ◽  
On Demand ◽  
Large Numbers ◽  
Genetic Modifications ◽  
Genome Scale

ABSTRACT Although only 6 years old, the CRISPR system has blossomed into a tool for rapid, on-demand genome engineering and gene regulation in Saccharomyces cerevisiae. In this minireview, we discuss fundamental CRISPR technologies, tools to improve the efficiency and capabilities of gene targeting, and cutting-edge techniques to explore gene editing and transcriptional regulation at genome scale using pooled approaches. The focus is on applications to metabolic engineering with topics including development of techniques to edit the genome in multiplex, tools to enable large numbers of genetic modifications using pooled single-guide RNA libraries and efforts to enable programmable transcriptional regulation using endonuclease-null Cas enzymes.

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