Search results for "Epigenetics"
showing 10 items of 517 documents
FISH and CHIPs: Colorful Clues to Radiation-Induced Chromosomal Instability
2004
Radiation produces a variety of clonal and non-clonal chromosome aberrations that can be characterized by fluorescence in situ hybridization (FISH). Epigenetic changes affecting the expression of an essential DNA repair gene(s) may be an importantant mechanism for radiation-induced chromosomal instability. Expression profiling with specialized cDNA chips promises to identify candidate genes for the delayed effects of radiation and to provide new insights into the manifold and complex cellular responses to DNA damage. Much progress can be made by using FISH and CHIPs to study the mechanisms and biological consequences of ionizing radiation.
Phylostratic Shift of Whole-Genome Duplications in Normal Mammalian Tissues towards Unicellularity Is Driven by Developmental Bivalent Genes and Reve…
2020
Tumours were recently revealed to undergo a phylostratic and phenotypic shift to unicellularity. As well, aggressive tumours are characterized by an increased proportion of polyploid cells. In order to investigate a possible shared causation of these two features, we performed a comparative phylostratigraphic analysis of ploidy-related genes, obtained from transcriptomic data for polyploid and diploid human and mouse tissues using pairwise cross-species transcriptome comparison and principal component analysis. Our results indicate that polyploidy shifts the evolutionary age balance of the expressed genes from the late metazoan phylostrata towards the upregulation of unicellular and early m…
Inducing Cold-Sensitivity in the Frigophilic Fly Drosophila montana by RNAi.
2016
Cold acclimation is a critical physiological adaptation for coping with seasonal cold. By increasing their cold tolerance individuals can remain active for longer at the onset of winter and can recover more quickly from a cold shock. In insects, despite many physiological studies, little is known about the genetic basis of cold acclimation. Recently, transcriptomic analyses in Drosophila virilis and D. montana revealed candidate genes for cold acclimation by identifying genes upregulated during exposure to cold. Here, we test the role of myo-inositol-1-phosphate synthase (Inos), in cold tolerance in D. montana using an RNAi approach. D. montana has a circumpolar distribution and overwinters…
A novel moniliformin derivative as pan-inhibitor of histone deacetylases triggering apoptosis of leukemia cells
2021
New and potent agents that evade multidrug resistance (MDR) and inhibit epigenetic modifications are of great interest in cancer drug development. Here, we describe that a moniliformin derivative (IUPAC name: 3-(naphthalen-2-ylsulfanyl)-4-{[(2Z)-1,3,3-trimethyl-2,3-dihydro-1H-indol-2-ylidene]methyl}cyclobut-3-ene-1,2-dione; code: MCC1381) bypasses P-gp-mediated MDR. Using transcriptomics, we identified a large number of genes significantly regulated in response to MCC1381, which affected the cell cycle and disturbed cellular death and survival. The potential targets of MCC1381 might be histone deacetylases (HDACs) as predicted by SwissTargetPrediction. In silico studies confirmed that MCC13…
Targeting multiple myeloma with natural polyphenols
2019
Multiple myeloma (MM) is still an incurable hematologic malignancy. Although new therapeutic strategies have been developed to target different pathways in malignant cells, such as proliferation, differentiation, and apoptosis, better survival rates have also been achieved by the introduction of autologous stem cell transplantation (ASCT). Hematopoietic stem cell transplantation and novel targeted agents, such as proteasome inhibitors, monoclonal antibodies, immunomodulatory drugs, check-point inhibitors and epigenetic modulators, have significantly achieved long remission time and increased survival rates. However, most patients relapse, develop resistance, and eventually die because of re…
Modulation of Cell Cycle Components by Epigenetic and Genetic Events
2005
Cell cycle progression is monitored by surveillance mechanisms, or cell cycle checkpoints, that ensure that initiation of a later event is coupled with the completion of an early cell cycle event. Deregulated proliferation is a characteristic feature of tumor cells. Moreover, defects in many of the molecules that regulate the cell cycle have been implicated in cancer formation and progression. Key among these are p53, the retinoblastoma protein (pRb) and its related proteins, p107 and pRb2/p130, and cdk inhibitors (p15, p16, p18, p19, p21, p27), all of which act to keep the cell cycle from progressing until all repairs to damaged DNA have been completed. The pRb (pRb/p16(INK4a)/cyclin D1) a…
Computational identification of cell-specific variable regions in ChIP-seq data.
2019
ABSTRACT Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is used to identify genome-wide DNA regions bound by proteins. Several sources of variation can affect the reproducibility of a particular ChIP-seq assay, which can lead to a misinterpretation of where the protein under investigation binds to the genome in a particular cell type. Given one ChIP-seq experiment with replicates, binding sites not observed in all the replicates will usually be interpreted as noise and discarded. However, the recent discovery of high-occupancy target (HOT) regions suggests that there are regions where binding of multiple transcription factors can be identified. To investigate these regions,…
Role of nuclear glutathione as a key regulator of cell proliferation.
2009
Glutathione (GSH) is essential for survival of eukaryotic but not in prokaryotic cells. Its functions in nucleated cells are far from being known. In fact GSH plays an important role in cell proliferation. The purpose of the present review is to summarize the relationship between glutathione and the important events that take place in the nucleus during the cell cycle. Most GSH co-localizes with nuclear DNA when cells are proliferating. However, when cells were confluent no differences between nucleus and cytoplasm could be seen. A number of relevant nuclear proteins are strictly dependent on nuclear redox status. For instance, we found that telomerase is regulated by shifts in glutathione …
Can Alzheimer disease be a form of type 3 diabetes?
2012
Alzheimer disease (AD) and metabolic syndrome are two highly prevalent pathological conditions of Western society due to incorrect diet, lifestyle, and vascular risk factors. Recent data have suggested metabolic syndrome as an independent risk factor for AD and pre-AD syndrome. Furthermore, biological plausibility for this relationship has been framed within the “metabolic cognitive syndrome” concept. Due to the increasing aging of populations, prevalence of AD in Western industrialized countries will rise in the near future. Thus, new knowledge in the area of molecular biology and epigenetics will probably help to make an early molecular diagnosis of dementia. An association between metabo…
Brains in metamorphosis: reprogramming cell identity within the central nervous system
2014
During embryonic development, uncommitted pluripotent cells undergo progressive epigenetic changes that lock them into a final differentiated state. Can mammalian cells change identity within the living organism? Direct lineage reprogramming of cells has attracted attention as a means to achieve organ regeneration. However, it is unclear whether cells in the CNS are endowed with the plasticity to reprogram. Neurons in particular are considered among the most immutable cell types, able to retain their class-specific traits for the lifespan of the organism. Here we focus on two experimental paradigms, glia-to-neuron and neuron-to-neuron conversion, to consider how lineage reprogramming has ch…