scholarly journals Functional role of histone variant Htz1 in the stress response to oleate in Saccharomyces cerevisiae

2015 ◽  
Vol 35 (4) ◽  
Author(s):  
Hongde Liu ◽  
Guanghui Li ◽  
Lingjie Liu ◽  
Yakun Wan

In response to oleate stress in Saccharomyces cerevisiaes, Histone Two A Z1 (Htz1) undergoes a global redistribution during the glucose-oleate shift. The number of Htz1-bound genes increases, but the number of Htz1-bound ribosome genes decreases with stress. Citrate cycle-associated genes are enhanced and ribosome genes are repressed. Nucleosome dynamics are coupled with Htz1-binding changes upon stress. Multicopy suppressor of SNF1 protein 2 (Msn2) acts an important role in response to the oleate stress. We highlight the dynamics of Htz1 in the oleate stress.

2017 ◽  
Vol 29 (4) ◽  
pp. 791-807 ◽  
Author(s):  
Weronika Sura ◽  
Michał Kabza ◽  
Wojciech M. Karlowski ◽  
Tomasz Bieluszewski ◽  
Marta Kus-Slowinska ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Deepika Prasad ◽  
Divya Arora ◽  
Vinay Kumar Nandicoori ◽  
K. Muniyappa

Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 578-590 ◽  
Author(s):  
Nick Powell ◽  
Eirini Pantazi ◽  
Polychronis Pavlidis ◽  
Anastasia Tsakmaki ◽  
Katherine Li ◽  
...  

ObjectiveThe functional role of interleukin-22 (IL22) in chronic inflammation is controversial, and mechanistic insights into how it regulates target tissue are lacking. In this study, we evaluated the functional role of IL22 in chronic colitis and probed mechanisms of IL22-mediated regulation of colonic epithelial cells.DesignTo investigate the functional role of IL22 in chronic colitis and how it regulates colonic epithelial cells, we employed a three-dimentional mini-gut epithelial organoid system, in vivo disease models and transcriptomic datasets in human IBD.ResultsAs well as inducing transcriptional modules implicated in antimicrobial responses, IL22 also coordinated an endoplasmic reticulum (ER) stress response transcriptional programme in colonic epithelial cells. In the colon of patients with active colonic Crohn’s disease (CD), there was enrichment of IL22-responsive transcriptional modules and ER stress response modules. Strikingly, in an IL22-dependent model of chronic colitis, targeting IL22 alleviated colonic epithelial ER stress and attenuated colitis. Pharmacological modulation of the ER stress response similarly impacted the severity of colitis. In patients with colonic CD, antibody blockade of IL12p40, which simultaneously blocks IL12 and IL23, the key upstream regulator of IL22 production, alleviated the colonic epithelial ER stress response.ConclusionsOur data challenge perceptions of IL22 as a predominantly beneficial cytokine in IBD and provide novel insights into the molecular mechanisms of IL22-mediated pathogenicity in chronic colitis. Targeting IL22-regulated pathways and alleviating colonic epithelial ER stress may represent promising therapeutic strategies in patients with colitis.Trial registration numberNCT02749630.


1998 ◽  
Vol 18 (12) ◽  
pp. 7383-7396 ◽  
Author(s):  
David A. Mangus ◽  
Nadia Amrani ◽  
Allan Jacobson

ABSTRACT The poly(A) tail of an mRNA is believed to influence the initiation of translation, and the rate at which the poly(A) tail is removed is thought to determine how fast an mRNA is degraded. One key factor associated with this 3′-end structure is the poly(A)-binding protein (Pab1p) encoded by the PAB1 gene inSaccharomyces cerevisiae. In an effort to learn more about the functional role of this protein, we used a two-hybrid screen to determine the factor(s) with which it interacts. We identified five genes encoding factors that specifically interact with the carboxy terminus of Pab1p. Of a total of 44 specific clones identified,PBP1 (for Pab1p-binding protein) was isolated 38 times. Of the putative interacting genes examined, PBP1 promoted the highest level of resistance to 3-aminotriazole (>100 mM) in constructs in which HIS3 was used as a reporter. We determined that a fraction of Pbp1p cosediments with polysomes in sucrose gradients and that its distribution is very similar to that of Pab1p. Disruption ofPBP1 showed that it is not essential for viability but can suppress the lethality associated with a PAB1 deletion. The suppression of pab1Δ by pbp1Δ appears to be different from that mediated by other pab1 suppressors, since disruption of PBP1 does not alter translation rates, affect accumulation of ribosomal subunits, change mRNA poly(A) tail lengths, or result in a defect in mRNA decay. Rather, Pbp1p appears to function in the nucleus to promote proper polyadenylation. In the absence of Pbp1p, 3′ termini of pre-mRNAs are properly cleaved but lack full-length poly(A) tails. These effects suggest that Pbp1p may act to repress the ability of Pab1p to negatively regulate polyadenylation.


2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Callum J. O’Kane ◽  
Edel M. Hyland

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.


2017 ◽  
Vol 8 ◽  
Author(s):  
Courtney A. Deck ◽  
Jamie L. Honeycutt ◽  
Eugene Cheung ◽  
Hannah M. Reynolds ◽  
Russell J. Borski

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2716
Author(s):  
Matteo Trovato ◽  
Vibha Patil ◽  
Maja Gehre ◽  
Kyung Min Noh

The systematic mutation of histone 3 (H3) genes in model organisms has proven to be a valuable tool to distinguish the functional role of histone residues. No system exists in mammalian cells to directly manipulate canonical histone H3 due to a large number of clustered and multi-loci histone genes. Over the years, oncogenic histone mutations in a subset of H3 have been identified in humans, and have advanced our understanding of the function of histone residues in health and disease. The oncogenic mutations are often found in one allele of the histone variant H3.3 genes, but they prompt severe changes in the epigenetic landscape of cells, and contribute to cancer development. Therefore, mutation approaches using H3.3 genes could be relevant to the determination of the functional role of histone residues in mammalian development without the replacement of canonical H3 genes. In this review, we describe the key findings from the H3 mutation studies in model organisms wherein the genetic replacement of canonical H3 is possible. We then turn our attention to H3.3 mutations in human cancers, and discuss H3.3 substitutions in the N-terminus, which were generated in order to explore the specific residue or associated post-translational modification.


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