scholarly journals Changes in Chromatin Organization Eradicate Cellular Stress Resilience to UVA/B Light and Induce Premature Aging

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1755
Author(s):  
Bela Vasileva ◽  
Dessislava Staneva ◽  
Natalia Krasteva ◽  
George Miloshev ◽  
Milena Georgieva
Keyword(s):  
Genome Stability ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Linker Histone ◽  
Chromatin Organization ◽  
Premature Aging ◽  
Yeast Cells ◽  
Nuclear Proteins ◽  
Chronological Aging ◽  
Linker Histones

Complex interactions among DNA and nuclear proteins maintain genome organization and stability. The nuclear proteins, particularly the histones, organize, compact, and preserve the stability of DNA, but also allow its dynamic reorganization whenever the nuclear processes require access to it. Five histone classes exist and they are evolutionarily conserved among eukaryotes. The linker histones are the fifth class and over time, their role in chromatin has been neglected. Linker histones interact with DNA and the other histones and thus sustain genome stability and nuclear organization. Saccharomyces cerevisiae is a brilliant model for studying linker histones as the gene for it is a single-copy and is non-essential. We, therefore, created a linker histone-free yeast strain using a knockout of the relevant gene and traced the way cells age chronologically. Here we present our results demonstrating that the altered chromatin dynamics during the chronological lifespan of the yeast cells with a mutation in ARP4 (the actin-related protein 4) and without the gene HHO1 for the linker histone leads to strong alterations in the gene expression profiles of a subset of genes involved in DNA repair and autophagy. The obtained results further prove that the yeast mutants have reduced survival upon UVA/B irradiation possibly due to the accelerated decompaction of chromatin and impaired proliferation. Our hypothesis posits that the higher-order chromatin structure and the interactions among chromatin proteins are crucial for the maintenance of chromatin organization during chronological aging under optimal and UVA-B stress conditions.

scholarly journals Transcriptional Repression by the Pho4 Transcription Factor Controls the Timing of SNZ1 Expression

2008 ◽  
Vol 7 (6) ◽  
pp. 949-957 ◽  
Author(s):  
Masafumi Nishizawa ◽  
Tae Komai ◽  
Nobuyuki Morohashi ◽  
Mitsuhiro Shimizu ◽  
Akio Toh-e
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Repression ◽  
Structural Changes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Nutrient Sensing ◽  
Yeast Cells ◽  
Diauxic Shift

ABSTRACT Nutrient-sensing kinases play important roles for the yeast Saccharomyces cerevisiae to adapt to new nutrient conditions when the nutrient status changes. Our previous global gene expression analysis revealed that the Pho85 kinase, one of the yeast nutrient-sensing kinases, is involved in the changes in gene expression profiles when yeast cells undergo a diauxic shift. We also found that the stationary phase-specific genes SNZ1 and SNO1, whch share a common promoter, are not properly induced when Pho85 is absent. To examine the role of the kinase in SNZ1/SNO1 regulation, we analyzed their expression during the growth of various yeast mutants, including those affecting Pho85 function or lacking the Pho4 transcription factor, an in vivo substrate of Pho85, and tested Pho4 binding by chromatin immunoprecipitation. Pho4 exhibits temporal binding to the SNZ1/SNO1 promoter to down-regulate the promoter activity, and a Δpho4 mutation advances the timing of SNZ1/SNO1 expression. SNZ2, another member of the SNZ/SNO family, is expressed at an earlier growth stage than SNZ1, and Pho4 does not affect this timing, although Pho85 is required for SNZ2 expression. Thus, Pho4 appears to regulate the different timing of the expression of the SNZ/SNO family members. Pho4 binding to the SNZ1/SNO1 promoter is accompanied by alterations in chromatin structure, and Rpd3 histone deacetylase is required for the proper timing of SNZ1/SNO1 expression, while Asf1 histone chaperone is indispensable for their expression. These results imply that Pho4 plays positive and negative roles in transcriptional regulation, with both cases involving structural changes in its target chromatin.

scholarly journals Global Gene Expression Analysis of Yeast Cells during Sake Brewing

2006 ◽  
Vol 72 (11) ◽  
pp. 7353-7358 ◽  
Author(s):  
Hong Wu ◽  
Xiaohong Zheng ◽  
Yoshio Araki ◽  
Hiroshi Sahara ◽  
Hiroshi Takagi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Analysis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Yeast Cells ◽  
Yeast Gene ◽  
High Concentration ◽  
Brewing Process ◽  
Global Gene Expression Analysis

ABSTRACT During the brewing of Japanese sake, Saccharomyces cerevisiae cells produce a high concentration of ethanol compared with other ethanol fermentation methods. We analyzed the gene expression profiles of yeast cells during sake brewing using DNA microarray analysis. This analysis revealed some characteristics of yeast gene expression during sake brewing and provided a scaffold for a molecular level understanding of the sake brewing process.

Characterisation of gene expression profiles of yeast cells expressing BRCA1 missense variants

2009 ◽  
Vol 45 (12) ◽  
pp. 2187-2196 ◽  
Author(s):  
Leontina Di Cecco ◽  
Erika Melissari ◽  
Veronica Mariotti ◽  
Caterina Iofrida ◽  
Alvaro Galli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Yeast Cells ◽  
Missense Variants

scholarly journals Suppression of DSB Formation by Polβ in Active DNA Demethylation is Required for Postnatal Hippocampal Development

2019 ◽  
Author(s):  
Akiko Uyeda ◽  
Kohei Onishi ◽  
Teruyoshi Hirayama ◽  
Satoko Hattori ◽  
Tsuyoshi Miyakawa ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Hippocampal Neurons ◽  
Genome Stability ◽  
Neuronal Development ◽  
Excision Repair ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Dna Demethylation ◽  
Spatial Learning And Memory ◽  
Active Dna Demethylation

AbstractGenome stability is essential for brain development and function. However, the contribution of DNA repair to genome stability in neurons remains elusive. Here, we demonstrate that the base excision repair protein Polβ is involved in hippocampal neuronal differentiation via a TET-mediated active DNA demethylation during early postnatal stages. Polβ deficiency induced extensive DNA double-strand breaks (DSBs) in hippocampal neurons, and a lesser extent in cortical neurons, during a period in which decreased levels of 5-methylcytosine were observed in genomic DNA. Inhibition of the hydroxylation of 5-methylcytosine by microRNAs miR29a/b-1 expression diminished DSB formation. Conversely, its induction by TET1 overexpression increased DSBs. The damaged hippocampal neurons exhibited aberrant neuronal gene expression profiles and dendrite formation. Behavioral analyses revealed impaired spatial learning and memory in adulthood. Thus, Polβ maintains genome stability in the active DNA demethylation that occurs during postnatal neuronal development, thereby contributing to differentiation and subsequent behavior.

scholarly journals Chromatin Structure Dynamics Preserve Genome Stability in Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1777-1777
Author(s):  
Antonis Kokkalis ◽  
Praveen Anand ◽  
Monica S. Nair ◽  
Johannes M. Waldschmidt ◽  
Julia Frede ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Cell Lines ◽  
Copy Number ◽  
Genome Stability ◽  
Replication Stress ◽  
Linker Histone ◽  
Myeloma Cells ◽  
Linker Histones ◽  
Low Pass

Introduction: Multiple myeloma (MM) is a genetically complex disease with extensive clonal heterogeneity. Substantial genomic instability in MM is illustrated by extensive copy number variations (CNVs) that can be detected in almost every MM patient. The molecular basis of this genomic instability in MM is not clear. Linker histones are dynamic components of chromatin and mutations in these molecules are present in ~6% of MM patients. Two of the linker histone super-family, HIST1H1Eand HIST1H1Care the most frequently mutated members of the family in MM and their mutations mostly occur in a clonal fashion. Interestingly, it has been reported in human cell lines and in other species that linker histone loss affects DNA damage/repair pathways and leads to transcription-replication conflicts. Based on these data we hypothesized that mutation or genomic loss of linker histones affects the genome stability of MM cells. To test this hypothesis, we developed an experimental system using CRISPR/Cas9 genome editing to generate MM linker histone-deficient cells. Low-pass whole genome sequencing (LPWGS), immunoblotting and immunofluorescent experiments were performed for genomic, molecular and functional characterization. We found that HIST1H1E,HIST1H1Cand H1FXwere the most abundantly expressed members of the linker histone family in primary myeloma cells and that myeloma cells have the highest dependency on HIST1H1Eand HIST1H1Cwhen compared to all other cancer cell lines derived from other tissues. We used OPM2 and U266 myeloma cell lines and generated knock-out variants of HIST1H1E, HIST1H1Cand H1FXlinker histones by inserting a biallelic stop codon, followed by generation of individual single-cell clones that were used as replicates. We first asked if linker histone deficient cells preserve genome stability. To address this question, we performed low pass whole genome sequencing and found more copy number abnormalities in linker histone deficient myeloma cells, when compared to wild-type cells. Moreover, linker histone deficient cells showed increased DNA damage as indicated by higher frequency of nuclear foci that were positive for damage dependent phosphorylation of the histone variant H2AX ( γH2AX). This was associated with an increased frequency of micronuclei in linker histones deficient cells, suggesting defects in mitotic fidelity and in genome stability. These micronuclei were positive for γH2AX by microscopic staining, indicative of DNA damage. We then asked if the DNA damage in micronuclei is due to defective and asynchronous DNA replication when the myeloma cells are exposed to etoposide, a topoisomerase inhibitor that induces DNA replication stress and double-strand DNA breaks (DSBs). Etoposide treatment of myeloma cells caused DNA replication stress, as measured by immunofluorescent staining of micronuclei for Replication Protein A (RPA). Conclusions: Our results demonstrate that loss of linker histones is associated with increased copy number abnormalities, extensive DNA damage and increased frequency of micronuclei, most likely as a consequence of replication stress. These data provide a potential mechanism of how chromatin structure dynamics preserve genome stability in myeloma cells. Disclosures Lohr: Celgene: Research Funding; T2 Biosystems: Honoraria.

scholarly journals A glitch in the snitch: the role of linker histone H1 in shaping the epigenome in normal and diseased cells

Open Biology ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 210124
Author(s):  
Ankita Saha ◽  
Yamini Dalal
Keyword(s):  
Transcription Factors ◽  
New Technologies ◽  
Harry Potter ◽  
Linker Histone ◽  
Chromatin Organization ◽  
Linker Histones ◽  
Positively Charged

Histone H1s or the linker histones are a family of dynamic chromatin compacting proteins that are essential for higher-order chromatin organization. These highly positively charged proteins were previously thought to function solely as repressors of transcription. However, over the last decade, there is a growing interest in understanding this multi-protein family, finding that not all variants act as repressors. Indeed, the H1 family members appear to have distinct affinities for chromatin and may potentially affect distinct functions. This would suggest a more nuanced contribution of H1 to chromatin organization. The advent of new technologies to probe H1 dynamics in vivo , combined with powerful computational biology, and in vitro imaging tools have greatly enhanced our knowledge of the mechanisms by which H1 interacts with chromatin. This family of proteins can be metaphorically compared to the Golden Snitch from the Harry Potter series, buzzing on and off several regions of the chromatin, in combat with competing transcription factors and chromatin remodellers, thereby critical to the epigenetic endgame on short and long temporal scales in the life of the nucleus. Here, we summarize recent efforts spanning structural, computational, genomic and genetic experiments which examine the linker histone as an unseen architect of chromatin fibre in normal and diseased cells and explore unanswered fundamental questions in the field.

scholarly journals Saccharomyces cerevisiaeLinker Histone—Hho1p Maintains Chromatin Loop Organization during Ageing

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Katya Uzunova ◽  
Milena Georgieva ◽  
George Miloshev
Keyword(s):  
Molecular Mechanisms ◽  
Cellular Level ◽  
Higher Order ◽  
Linker Histone ◽  
Yeast Cells ◽  
Chromatin Loop ◽  
Cellular Functions ◽  
Linker Histones ◽  
Chronological Lifespan ◽  
Whole Process

Intricate, dynamic, and absolutely unavoidable ageing affects cells and organisms through their entire lifetime. Driven by diverse mechanisms all leading to compromised cellular functions and finally to death, this process is a challenge for researchers. The molecular mechanisms, the general rules that it follows, and the complex interplay at a molecular and cellular level are yet little understood. Here, we present our results showing a connection between the linker histones, the higher-order chromatin structures, and the process of chronological lifespan of yeast cells. By deleting the gene for the linker histone inSaccharomyces cerevisiaewe have created a model for studying the role of chromatin structures mainly at its most elusive and so far barely understood higher-order levels of compaction in the processes of yeast chronological lifespan. The mutant cells demonstrated controversial features showing slower growth than the wild type combined with better survival during the whole process. The analysis of the global chromatin organization during different time points demonstrated certain loss of the upper levels of chromatin compaction in the cells without linker histone. The results underlay the importance of this histone for the maintenance of the chromatin loop structures during ageing.

scholarly journals Data mining of Gene expression profiles of Saccharomyces cerevisiae in response to mild heat stress response

2014 ◽  
Author(s):  
Kaiyuan Ji ◽  
Wenli Ma ◽  
Wenling Zheng
Keyword(s):  
Gene Expression ◽  
Heat Stress ◽  
Expression Profiles ◽  
Model Organism ◽  
Gene Expression Profiles ◽  
Time Frame ◽  
Yeast Cells ◽  
Nucleic Acid Metabolism ◽  
Biological Processes ◽  
Heat Stress Response

We chose yeast as a model organism to explore how eukaryotic cells respond to heat stress. This study provides details on the way yeast responds to temperature changes and is therefore an empirical reference for basic cell research and industrial fermentation of yeast. We use the Qlucore Omics Explorer (QOE) bioinformatics software to analyze the gene expression profiles of the heat stress from Gene Expression Omnibus (GEO). Genes and their expression are listed in heat maps, and the gene function is analyzed against the biological processes and pathways. We can find that the expression of genes changed over time after heat stress. Gene expression changed rapidly from 0 min to 60 min after heat shock, and gene expression stabilized between 60 min to 360 min. The yeast cells begin to adjust themselves to the high temperatures in terms of the level of gene expression at about 60 min. In all of the involved pathways and biological processes, those related to ribosome and nucleic acid metabolism declined in about 15?30 min and those related to starch and sucrose increased in the same time frame. Temperature can be a simple way to control the biological processes and pathways of cell.

1327: Gene Expression Profiles in Benign Prostatic Hyperplasia

2004 ◽  
Vol 171 (4S) ◽  
pp. 349-350
Author(s):  
Gaelle Fromont ◽  
Michel Vidaud ◽  
Alain Latil ◽  
Guy Vallancien ◽  
Pierre Validire ◽  
...  
Keyword(s):  
Gene Expression ◽  
Benign Prostatic Hyperplasia ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Prostatic Hyperplasia
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