scholarly journals Locus-specific induction of gene expression from heterochromatin loci during cellular senescence

Nature Aging ◽  
2021 ◽  
Author(s):  
Kosuke Tomimatsu ◽  
Dóra Bihary ◽  
Ioana Olan ◽  
Aled J. Parry ◽  
Stefan Schoenfelder ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cellular Senescence ◽  
Specific Induction

Epigenetic control of cellular senescence in disease: opportunities for therapeutic intervention

2007 ◽  
Vol 9 (7) ◽  
pp. 1-26 ◽  
Author(s):  
Stuart P. Atkinson ◽  
W. Nicol Keith
Keyword(s):  
Gene Expression ◽  
Cellular Senescence ◽  
Chromatin Remodelling ◽  
Telomere Maintenance ◽  
Cell Physiology ◽  
Gene Promoters ◽  
Epigenetic Mechanisms ◽  
Histone Proteins ◽  
Regulate Gene Expression ◽  
Regulate Gene

AbstractUnderstanding how senescence is established and maintained is an important area of study both for normal cell physiology and in tumourigenesis. Modifications to N-terminal tails of histone proteins, which can lead to chromatin remodelling, appear to be key to the regulation of the senescence phenotype. Epigenetic mechanisms such as modification of histone proteins have been shown to be sufficient to regulate gene expression levels and specific gene promoters can become epigenetically altered at senescence. This suggests that epigenetic mechanisms are important in senescence and further suggests epigenetic deregulation could play an important role in the bypass of senescence and the acquisition of a tumourigenic phenotype. Tumour suppressor proteins and cellular senescence are intimately linked and such proteins are now known to regulate gene expression through chromatin remodelling, again suggesting a link between chromatin modification and cellular senescence. Telomere dynamics and the expression of the telomerase genes are also both implicitly linked to senescence and tumourigenesis, and epigenetic deregulation of the telomerase gene promoters has been identified as a possible mechanism for the activation of telomere maintenance mechanisms in cancer. Recent studies have also suggested that epigenetic deregulation in stem cells could play an important role in carcinogenesis, and new models have been suggested for the attainment of tumourigenesis and bypass of senescence. Overall, proper regulation of the chromatin environment is suggested to have an important role in the senescence pathway, such that its deregulation could lead to tumourigenesis.

scholarly journals HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci

2016 ◽  
Vol 215 (3) ◽  
pp. 325-334 ◽  
Author(s):  
Katherine M. Aird ◽  
Osamu Iwasaki ◽  
Andrew V. Kossenkov ◽  
Hideki Tanizawa ◽  
Nail Fatkhutdinov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Growth ◽  
Cellular Senescence ◽  
Growth Arrest ◽  
High Mobility ◽  
Cell Growth Arrest ◽  
Cytokines And Chemokines ◽  
Secreted Factors ◽  
Genes Encoding ◽  
Secretory Phenotype

Cellular senescence is a stable cell growth arrest that is characterized by the silencing of proliferation-promoting genes through compaction of chromosomes into senescence-associated heterochromatin foci (SAHF). Paradoxically, senescence is also accompanied by increased transcription of certain genes encoding for secreted factors such as cytokines and chemokines, known as the senescence-associated secretory phenotype (SASP). How SASP genes are excluded from SAHF-mediated global gene silencing remains unclear. In this study, we report that high mobility group box 2 (HMGB2) orchestrates the chromatin landscape of SASP gene loci. HMGB2 preferentially localizes to SASP gene loci during senescence. Loss of HMGB2 during senescence blunts SASP gene expression by allowing for spreading of repressive heterochromatin into SASP gene loci. This correlates with incorporation of SASP gene loci into SAHF. Our results establish HMGB2 as a novel master regulator that orchestrates SASP through prevention of heterochromatin spreading to allow for exclusion of SASP gene loci from a global heterochromatin environment during senescence.

Altered gene expression during cellular aging

Genome ◽  
1989 ◽  
Vol 31 (1) ◽  
pp. 386-389 ◽  
Author(s):  
James R. Smith ◽  
Olivia M. Pereira-Smith
Keyword(s):  
Gene Expression ◽  
Dna Synthesis ◽  
Cell Lines ◽  
Cellular Senescence ◽  
Human Cell ◽  
Messenger Rna ◽  
Human Cells ◽  
Cellular Aging ◽  
Human Cell Lines ◽  
Normal Human

The limited division potential of normal human diploid fibroblasts in culture represents a model system for cellular aging. Observations indicate cellular senescence is an active process. Senescent cells, although unable to divide, are actively metabolizing. Hybrids from fusion of normal and immortal human cells exhibit limited division potential, suggesting that the phenotype of cellular senescence is dominant and supporting the hypothesis that senescence is genetically programmed. Fusion of immortal human cell lines with each other has identified four complementation groups for indefinite division. This indicates that a limited number of specific genes or processes are involved in senescence. Senescent cells express highly abundant DNA synthesis inhibitory messenger RNAs and produce a surface membrane associated protein inhibitor of DNA synthesis not expressed in young cells. Senescent cell membranes were used as immunogen to generate three monoclonal antibodies reacting specifically with senescent but not young cells in several normal human cell lines. We have also found that fibronectin messenger RNA accumulates to high levels in senescent cells. The role of these changes in gene expression in senescence is being explored.Key words: cellular senescence, human cells.

scholarly journals Posttranscriptional gene regulation by RNA-binding proteins during oxidative stress: implications for cellular senescence

2008 ◽  
Vol 389 (3) ◽  
pp. 243-255 ◽  
Author(s):  
Kotb Abdelmohsen ◽  
Yuki Kuwano ◽  
Hyeon Ho Kim ◽  
Myriam Gorospe
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Cellular Senescence ◽  
Mammalian Cells ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Oxidant Damage ◽  
Regulated Gene Expression

AbstractTo respond adequately to oxidative stress, mammalian cells elicit rapid and tightly controlled changes in gene expression patterns. Besides alterations in the subsets of transcribed genes, two posttranscriptional processes prominently influence the oxidant-triggered gene expression programs: mRNA turnover and translation. Here, we review recent progress in our knowledge of theturnover andtranslationregulatory (TTR) mRNA-bindingproteins (RBPs) that influence gene expression in response to oxidative damage. Specifically, we identify oxidant damage-regulated mRNAs that are targets of TTR-RBPs, we review the oxidant-triggered signaling pathways that govern TTR-RBP function, and we examine emerging evidence that TTR-RBP activity is altered with senescence and aging. Given the potent influence of TTR-RBPs upon oxidant-regulated gene expression profiles, we propose that the senescence-associated changes in TTR-RBPs directly contribute to the impaired responses to oxidant damage that characterize cellular senescence and advancing age.

Histone gene expression remains coupled to DNA synthesis during in vitro cellular senescence

1987 ◽  
Vol 172 (2) ◽  
pp. 397-403 ◽  
Author(s):  
Gerard Zambetti ◽  
Robert Dell'Orco ◽  
Gary Stein ◽  
Janet Stein
Keyword(s):  
Gene Expression ◽  
Dna Synthesis ◽  
Cellular Senescence ◽  
Histone Gene ◽  
Histone Gene Expression

scholarly journals Gene expression in Lucilia sericata (Diptera: Calliphoridae) larvae exposed to Pseudomonas aeruginosa and Acinetobacter baumanii identifies shared and microbe-specific induction of immune genes

2021 ◽  
Author(s):  
Claire H McKenna ◽  
Danial Asgari ◽  
Tawni C Crippen ◽  
Le Zheng ◽  
Ronald A Sherman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Pathogenic Bacteria ◽  
Molecular Level ◽  
Lucilia Sericata ◽  
Acinetobacter Baumanii ◽  
Wound Debridement ◽  
Immune Genes ◽  
Specific Induction ◽  
Deficiency Gene

Antibiotic resistance is a continuing challenge in medicine. There are various strategies for expanding antibiotic therapeutic repertoires, including the use of blow flies. Their larvae exhibit strong antibiotic and antibiofilm properties that alter microbiome communities. One species, Lucilia sericata, is used to treat problematic wounds due to its debridement capabilities and its excretions and secretions that kill some pathogenic bacteria. There is much to be learned about how L. sericata interacts with microbiomes at the molecular level. To address this deficiency, gene expression was assessed after feeding exposure (1 hour or 4 hours) to two clinically problematic pathogens: Pseudomonas aeruginosa and Acinetobacter baumanii. The results identified immunity related genes that were differentially expressed when exposed to these pathogens, as well as non-immune genes possibly involved in gut responses to bacterial infection. There was a greater response to P. aeruginosa that increased over time, while few genes responded to A. baumanii exposure and expression was not time-dependent. The response to feeding on pathogens indicates a few common responses and features distinct to each pathogen, which is useful in improving wound debridement therapy and helps develop biomimetic alternatives.

Sign in / Sign up

Export Citation Format

Share Document