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Chromatin, histones, and epigenetic tagsKoutzamani, Elisavet January 2006 (has links)
The fundamental building blocks of chromatin are the nucleosomes. Each such unit is composed of about 200 bp of DNA, the well-conserved core histones (H2A, H2B, H3 and H4) and a linker histone (H1). The DNA is wound around two dimers of H2A–H2B and a tetramer comprising two molecules each of H3 and H4, and there is approximately one linker histone molecule positioned on the exterior of the DNA–protein octamer complex. The nucleosome directs the various structural transitions in chromatin that are needed for proper transcriptional regulation during differentiation and development of the organism in question. The gene activity can be regulated by different histone variants, DNA–protein interactions, and protein–protein interactions, all of which are influenced by the enormous amounts of post-translational modifications that occur in the histone tails. The research underlying this thesis focused on different aspects of post-translational modifications during aging, differentiation, and progression of the cell cycle, and also on expression of linker histone variants and linker histone-chromatin interactions in a variety of cells and tissues. The present results are the first to show that H4 can be trimethylated at lysine 20 in mammalian cells. The trimethylated H4K20 was found in rat kidney and liver at levels that rose with increasing age of the nimals, and it was also detected in trace amounts in human cell lines. Furthermore, in differentiating MEL cells, trimethylated H4K20 was localized to heterochromatin, and levels of trimethylated H4K20 increased during the course of cell differentiation and were correlated with the increasing compaction of the chromatin. The chromatin of terminally differentiated chicken and frog erythrocytes is highly condensed, and the linker histone variants it contains vary between the two species. Cytofluorometric analyses revealed that the linker histones in the chicken erythrocytes exhibited higher affinity for chromatin than did those in the frog erythrocytes. Characterization of the H1° in frog erythrocytes proved it to be the H1°-2 subvariant. Other experiments demonstrated that normal human B lymphocytes expressed the linker histone variants H1.2, H1.3, H1.4, and H1.5, and that B cells from patients with B-CLL expressed the same variants although in different amounts. The most striking dissimilarity was that amounts of H1.3 in the cells were decreased or undetectable in some samples. Sequencing did not discern any defects in the H1.3 gene, and thus the absence of H1.3 is probably regulated at the post-translational level. It was also observed that the levels of linker histone phosphorylation in EBV-transformed B lymphocytes were already increased in the G1 phase of the cell cycle, which is earlier than previously thought. This increase in phosphorylation is probably responsible for the lower affinity of linker histones for chromatin in EBV-transformed cells in the G1 phase of the cell cycle.
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Histone modifications and their role in splicingWettermark, Anna January 2020 (has links)
Splicing is the process when introns gets removed and exons are spliced together. This is an important step to form a clean mRNA with no unnecessary sequences that could interrupt protein synthesis. There are different types of splicing and some of them need a complex called spliceosome. The spliceosome requires ATP, small nuclear RNAs and splicing factors. The spliceosome and the process splicing can be regulated by epigenetics, and one epigenetic mechanism is histone modification. There are four types of histone modifications; methylation, phosphorylation, ubiquitination and acetylation. They regulate splicing to different extents by altering the chromatin structure, affect the assembly of the spliceosome and regulate the attraction of splicing factors. This review will investigate if histone modifications affect splicing and to what extent. Suggestions for further research regarding the relationship between splicing and histone modifications will also be provided. The review is based on 30 articles and two books and the search was conducted between 30th of March 2020 and 13th of April 2020. Ubiquitination and phosphorylation have a minor effect on splicing meanwhile methylation and acetylation affect splicing in great extent.
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Chromatin Modified! Dynamics, Mechanics, Structure, and HIV IntegrationSimon, Marek 20 June 2012 (has links)
No description available.
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