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Signal transduction and exercise
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Brendan Egan, Adam P. Sharples
Epigenetic regulation of gene expression is briefly introduced in Chapter 3 and a full chapter in this textbook is dedicated to epigenetics of exercise (Chapter 6), but given the importance of chromatin remodelling and modulation of DNA methylation as part of the signal transduction model, we will briefly cover the topic in this chapter too. The DNA in the human genome has been estimated to be almost 2 m long. In order to fit into a tiny nucleus of only 10 micrometres, it must be very tightly packaged. This DNA packaging is achieved by wrapping DNA around complexes which are built from eight histone proteins. DNA together with histone complexes is termed chromatin and the DNA wrapped around one histone complex is called a nucleosome.
Role of Histone Methyltransferase in Breast Cancer
Published in Meenu Gupta, Rachna Jain, Arun Solanki, Fadi Al-Turjman, Cancer Prediction for Industrial IoT 4.0: A Machine Learning Perspective, 2021
Surekha Manhas, Zaved Ahmed Khan
During DNA packaging, basic proteins – histones – play a reported mark as a chromatin component in the nucleus of eukaryote cells, where they bind with DNA and further proceed the DNA for packaging into smaller units designated as nucleosomes that display their role in gene regulation. The unwounded chromosomal DNA length varies. Diploid cell DNA of humans is about 1.8 meters, shows wounded association on the basic proteins, and has approximately 0.09 mm (90 micrometers) of chromatin. During the mitotic process, the human diploid cell undergoes condensation and duplication, resulting in about 120 mm of chromosome. Histone modifications are directly correlated with gene regulation functions, including ADP-ribosylation, methylation, acetylation, ubiquitination, and citrullination.
Enzyme Kinetics and Drugs as Enzyme Inhibitors
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Feinberg and Vogelstein (1983) were the first who detected that DNA of cancer cells are hypomethylated, a finding suggesting that not only genetic but also epigenetic alterations contribute to the development of cancer and other diseases. Because all cells in a multicellular organism contain the same DNA equipment there must be a regulatory process that guarantees the expression of genes required for a specific cell type. Hence apart from an analysis of the genome, knowledge about the epigenome, the entirety of the chemical changes of DNA and histone proteins of an organism is essential to be able to answer whether and if so and how often distinct genes are accessible to transcription enzymes as a prerequisite for the subsequent protein biosynthesis. This means that cell identity relies on epigenetic regulatory mechanisms of which one is the density of DNA packaging into chromatin. With a change of the epigenome cells answer to changes in their environment—an economic alternative to modifying the nucleotide sequence of genes. Research in the field of epigenetic processes such as DNA methylation, histone modifications, RNA interference shed light on the relationships between genotype and phenotype (Biémont, 2010).
Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma
Published in Journal of Extracellular Vesicles, 2018
Tatyana Vagner, Cristiana Spinelli, Valentina R. Minciacchi, Leonora Balaj, Mandana Zandian, Andrew Conley, Andries Zijlstra, Michael R. Freeman, Francesca Demichelis, Subhajyoti De, Edwin M. Posadas, Hisashi Tanaka, Dolores Di Vizio
We were aware that DNA may be fragmented during DNA extraction [33] and that the working range of the Bioanalyzer chip used in the above experiments is limited in measuring DNA fragments larger than 10,000 bp. Therefore, in order to determine the size of un-sheared vesicular DNA, we lysed EVs directly in agarose plugs and resolved EV DNA by PFGE [26]. Resolution of high molecular weight DNA, which was possible with this method, revealed that L-EVs contain DNA fragments up to 2 Mega base pair (Mbp) (Figure 2(a)). In addition, DNA fragments in the size range of 100 Kbp–2 Mbp were enriched in L-EVs compared to whole cells and were undetectable in S-EVs (Figure 2(a,b)). This suggests a distinct process of DNA packaging in L-EVs. Resolution of lower molecular weight DNA using the same method demonstrated that the DNA extracted with the kit exhibited significantly smaller size (~10 kbp) than the un-sheared DNA extracted in agarose plugs, suggesting that the use of a commercial kit for DNA extraction shreds the DNA (Figure 2(c)).
Does genome organization matter in spermatozoa? A refined hypothesis to awaken the silent vessel
Published in Systems Biology in Reproductive Medicine, 2018
Dimitrios Ioannou, Helen G. Tempest
The fact that the genome is highly organized should not come as a surprise, if the entire human genome is unraveled and disassociated from histones it is almost 2 meters in length, this has to be packaged into a micrometer nucleus in a way that permits a myriad of normal cellular functions (e.g., DNA replication, DNA transcription, DNA damage recognition and repair) (Fraser et al. 2015). The first step in the organization and condensation of DNA occurs when DNA wraps itself around histone complexes to form nucleosomes, these nucleosomes are condensed to form solenoids, and these solenoids are further packaged into kilobase loops or domains. Epigenetic modifications further condense or decondense DNA packaging depending on the requirements for each specific cell-type. A higher order organization of chromatin is further achieved by packaging chromosomes into discrete territories known as chromosome territories (CTs) that occupy cell-type specific nuclear addresses (Meaburn and Misteli 2007).
A comparative evaluation of migration sedimentation method for sperm preparation
Published in Systems Biology in Reproductive Medicine, 2018
Sevil Kiratli, Mehmet Yuncu, Kenan Kose, Sinan Ozkavukcu
Eliminating sperm with persistent histones is another goal of sperm preparation in ART. Persisted histones express an immaturity of DNA packaging which may have epigenetic consequences [Gannon et al. 2014; Siklenka et al. 2015; Urdinguio et al. 2015] and increased risk of DNA fragmentation [Hamad et al. 2014]. Colleu et al. [1996] demonstrated that sperm with advanced nuclear maturation were successfully selected following both DGC and SU, but more effectively after DGC. In a comprehensive study, Sánchez et al. [1994] compared SU, DGC, glass wool column filtration and MS methods, evaluating nuclear maturation of sperm by aniline blue staining and detected that glass wool column filtration and MS methods obtain the lowest percentage of sperm with persistent histones. In our study we show, using MS, sperm with persistent histones (Figure 5) were effectively eliminated in a way comparable to the combination of DGC+SU. The rate of persistent histones in the prepared sperm was 10.59±13.40% in the DGC+SU group, while 8.86±7.89% in the MS group (n=22). There was no significant difference between groups for persistent histones (p=0.613) (Table 2).