Search results for "Epigenetics"
showing 10 items of 517 documents
The mRNA degradation factor Xrn1 regulates transcription elongation in parallel to Ccr4
2019
Abstract Co-transcriptional imprinting of mRNA by Rpb4 and Rpb7 subunits of RNA polymerase II (RNAPII) and by the Ccr4–Not complex conditions its post-transcriptional fate. In turn, mRNA degradation factors like Xrn1 are able to influence RNAPII-dependent transcription, making a feedback loop that contributes to mRNA homeostasis. In this work, we have used repressible yeast GAL genes to perform accurate measurements of transcription and mRNA degradation in a set of mutants. This genetic analysis uncovered a link from mRNA decay to transcription elongation. We combined this experimental approach with computational multi-agent modelling and tested different possibilities of Xrn1 and Ccr4 acti…
The distribution of active RNA polymerase II along the transcribed region is gene-specific and controlled by elongation factors.
2010
In order to study the intragenic profiles of active transcription, we determined the relative levels of active RNA polymerase II present at the 3'- and 5'-ends of 261 yeast genes by run-on. The results obtained indicate that the 3'/5' run-on ratio varies among the genes studied by over 12 log(2) units. This ratio seems to be an intrinsic characteristic of each transcriptional unit and does not significantly correlate with gene length, G + C content or level of expression. The correlation between the 3'/5' RNA polymerase II ratios measured by run-on and those obtained by chromatin immunoprecipitation is poor, although the genes encoding ribosomal proteins present exceptionally low ratios in …
Salivary inflammatory proteins in patients with oral potentially malignant disorders
2019
Cytokines are a group of small proteins involved in the regulation of infection, immune responses and inflammation. Since altered cytokine responsiveness has been linked to Oral Squamous Cell Carcinoma (OSCC), research to date indicates the possibility of using salivary pro- and anti-inflammatory proteins for screening of oral disorders. OSCC is a multistep neoplasia in which many genetic and epigenetic changes have been correlated to cancerous transformation of oral potentially malignant disorders (OPMD) such as oral leukoplakia, erythroplakia and lichen planus. The goal of the innovative salivary diagnostics is the identification of a single or multiple biomarkers that will serve as a cli…
Oxidative Stress and the Epigenetics of Cell Senescence: Insights from Progeroid Syndromes.
2019
Background: Cell senescence constitutes a critical process to respond to a variety of insults and adverse circumstances. Senescence involves the detention of DNA replication and cell proliferation, and hence, genetic programs associated with DNA damage response, chromosome stability, chromatin rearrangement, epigenetic reprogramming, and cell cycle are tightly linked to the senescent phenotype. Although senescence increases with age, the real implication of senescence regulation in the progress of aging in humans is largely discussed. In this context, reactive oxygen species (ROS) accumulation has also been postulated to play a critical role in cell homeostasis, aging processes, and contro…
Npl3 stabilizes R-loops at telomeres to prevent accelerated replicative senescence.
2019
Abstract Telomere shortening rates must be regulated to prevent premature replicative senescence. TERRA R‐loops become stabilized at critically short telomeres to promote their elongation through homology‐directed repair (HDR), thereby counteracting senescence onset. Using a non‐bias proteomic approach to detect telomere binding factors, we identified Npl3, an RNA‐binding protein previously implicated in multiple RNA biogenesis processes. Using chromatin immunoprecipitation and RNA immunoprecipitation, we demonstrate that Npl3 interacts with TERRA and telomeres. Furthermore, we show that Npl3 associates with telomeres in an R‐loop‐dependent manner, as changes in R‐loop levels, for example, …
Histone Variant MacroH2A1 Marks Liver Aging and Orchestrates the Escape from Senescence Induced by DNA Hypomethylation in Hepatocellular Carcinoma
2015
The epigenetic basis of age-associated progression of liver diseases towards hepatocellular carcinoma (HCC) is unclear. MacroH2A1 is a variant of histone H2A1, present in the two isoforms, with fundamental roles in cell homeostasis. MacroH2A1 is a marker of senescence associated heterochromatic foci (SAHF) and synergizes with DNA demethylating chemotherapic agent 5-aza-2'-deoxycytidine (5-aza-dC) in silencing tumor suppressor genes in human fibroblasts. We show that protein levels of macroH2A1 isoforms are increased in the livers of old rodents and humans, and in human HCC tissue. Human HCC cells overexpressing macroH2A1 escape a 5-aza-dC-induced senescent phenotype, as determined by cell p…
The Expanding Constellation of Histone Post-Translational Modifications in the Epigenetic Landscape
2021
The emergence of a nucleosome-based chromatin structure accompanied the evolutionary transition from prokaryotes to eukaryotes. In this scenario, histones became the heart of the complex and precisely timed coordination between chromatin architecture and functions during adaptive responses to environmental influence by means of epigenetic mechanisms. Notably, such an epigenetic machinery involves an overwhelming number of post-translational modifications at multiple residues of core and linker histones. This review aims to comprehensively describe old and recent evidence in this exciting field of research. In particular, histone post-translational modification establishing/removal mechanism…
Epigenetic agents as an adjunct to active chemotherapy in hematological tumor cell lines
2012
Epigenetic therapy is a new promising area in cancer research that is based on the use of a series of molecules capable of affecting tumor cell growth, differentiation and death by modifying the cellular mechanisms underlying the control of gene expression. Significant enhancement of traditional anticancer drug effects has been also reported by several authors. Our recent research focused on the identification of new epigenetic agent-containing drug combinations to be employed in the therapy of leukemia. The results showed that the new combination of an histone deacetylase (HDAC) inhibitor and the ribonucleotide reductase (RR) inhibitor 3’-methyl-adenosine (3’-Me-Ado) is endowed with a sign…
Nutraceuticals and Functional Foods. Experimental research as a means for the innovation of already existing products: reporting of a type case.
2023
Innovation and the creation of new products in a company, or in a food industry, is an expensive process and requires profound transformations of the production processes. For this reason, the governance of some businesses often gives up on the idea of innovating, especially if some of their products, driving the market, can ensure short and medium-term earnings security. It is also quite well known, however, that the long-term solidity of a company is ensured only by innovation: mediating between these two possibilities is very difficult but one sustainable possibility, today, may consist in functionalizing already existing food products, adding, in the industrial manufacturing process, bi…
RB, epigenetic changes and chromosomal alterations in human primary fibroblasts in culture
2008
The regulation of chromatin structure is a dynamic and complex process modulated by epigenetic mechanisms. Epigenetic changes as malfunctioning of histone modifications and DNA methylation could affect several different cellular processes like regulation of gene transcription and could compromise the correct chromosome condensation and segregation. Is important to note that these alterations have been correlated with cancer initiation/progression. In particular hypomethylation of pericentromeric regions, usually methylated, has been associated to chromosomal instability, as well as hypermethylation of promoter CpG islands of tumor suppressor genes (p16, CHFR, BRCA1) is considered a cause of…