Search results for "Epigenesis"
showing 10 items of 225 documents
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…
Molecular diagnosis and therapy of hepatocellular carcinoma (HCC): an emerging field for advanced technologies.
2011
Despite great progress in diagnosis and management of hepatocellular carcinoma (HCC), the exact biology of the tumor remains poorly understood overall limiting the patients' outcome. Detailed analysis and characterization of the molecular mechanisms and subsequently individual prediction of corresponding prognostic traits would revolutionize both diagnosis and treatment of HCC and is the key goal of modern personalized medicine. Over the recent years systematic approaches for the analysis of whole tumor genomes and transcriptomes as well as epigenomes became affordable tools in translational research. This includes simultaneous analyses of thousands of molecular targets using microarray-bas…
Nuclear-mitochondrial interaction.
2007
The biogenesis of mitochondria depends on the coordinated expression of nuclear and mitochondrial genomes. Consequently, the control of mitochondrial biogenesis and function depends on extremely complex processes requiring a variety of well orchestrated regulatory mechanisms. It is clear that the interplay of transcription factors and coactivators contributes to the expression of both nuclear and mitochondrial respiratory genes. In addition, the regulation of mitochondria biogenesis depends on proteins that, interacting with messenger RNAs for mitochondrial proteins, influence their metabolism and expression. Moreover, a tight regulation of the import and final assembly of mitochondrial pro…
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…
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 …
An essential switch in subunit composition of a chromatin remodeling complex during neural development.
2007
Summary Mammalian neural stem cells (NSCs) have the capacity to both self-renew and to generate all the neuronal and glial cell-types of the adult nervous system. Global chromatin changes accompany the transition from proliferating NSCs to committed neuronal lineages, but the mechanisms involved have been unclear. Using a proteomics approach, we show that a switch in subunit composition of neural, ATP-dependent SWI/SNF-like chromatin remodeling complexes accompanies this developmental transition. Proliferating neural stem and progenitor cells express complexes in which BAF45a, a Kruppel/PHD domain protein and the actin-related protein BAF53a are quantitatively associated with the SWI2/SNF2-…
Immunotherapy With Human Gamma Delta T Cells—Synergistic Potential of Epigenetic Drugs?
2018
Epigenetics has emerged as one of the fastest growing concepts, adding more than 45 new publications every day, spreading through various fields ( 1). Conrad Waddington coined the term “epigenetics” in 1942; however, a multitude of definitions has been endorsed by different researchers. In essence, Waddington’s definition of “epigenetics” and its redefinition by Holiday is at the heart of cellular function. Hence, it is obvious that epigenetic regulation plays a central role also in the specification, differentiation, and functional plasticity of T lymphocytes ( 2). T-cell fate decision in progenitor cells, functional CD4 T-cell plasticity, CD8 T-cell differentiation, but also T-cell memory…
Chreod.
2020
The concept of chreod was introduced in 1957 by the English theoretical biologist Conrad Hal Waddington (cf. Waddington: 1957; Galperin: 2008). From a linguistic point of view, the word “chreod” is a neologism, or, more precisely, a compound formed by the combination of two Greek words: the verb chre- (“it is necessary, must”) and the substantive -hodos (“way, road”). Therefore, it means literally “obliged pathway” (cf. Fabris 2018: 252, n. 6). Of course, such an etymology covers only a little bit of the semantic repertoire deployed by chreod. But, it is however true that some aspects of the biology of living systems can be described in these terms. Indeed, at the most general level, the id…
Epigenetic Transcriptional Regulation of the Growth Arrest-Specific gene 1 (Gas1) in Hepatic Cell Proliferation at Mononucleosomal Resolution
2011
Background Gas1 (growth arrest-specific 1) gene is known to inhibit cell proliferation in a variety of models, but its possible implication in regulating quiescence in adult tissues has not been examined to date. The knowledge of how Gas1 is regulated in quiescence may contribute to understand the deregulation occurring in neoplastic diseases. Methodology/Principal Findings Gas1 expression has been studied in quiescent murine liver and during the naturally synchronized cell proliferation after partial hepatectomy. Chromatin immunoprecipitation at nucleosomal resolution (Nuc-ChIP) has been used to carry out the study preserving the in vivo conditions. Transcription has been assessed at real …
An omics perspective to the molecular mechanisms of anticancer metallo-drugs in the computational microscope era
2017
Introduction: Metallo-drugs have attracted enormous interest for cancer treatment. The achievements of this drug-type are summarized by the success story of cisplatin. That being said, there have been many drawbacks with its clinical use, which prompted decades worth of research efforts to move towards safer and more effective agents, either containing platinum or different metals. Areas covered: In this review, the authors provide an atomistic picture of the molecular mechanisms involving selected metallo-drugs from structural and molecular simulation studies. They also provide an omics perspective, pointing out many unsettled aspects of the most relevant families of metallo-drugs at an ep…