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Connections between intermediary metabolism and acetylation of histones
Zach, Róbert ; Převorovský, Martin (advisor) ; Bieberstein, Nicole (referee)
Acetylation of histone proteins affects chromatin structure and functions as a coactivating signal for transcription. Acetylation of histone lysine residues is mediated by histone acetyltransferases, which utilize molecule of Ac-CoA as a donor of acetyl group. Ac-CoA is located in the centre of intermediary carbon metabolism, where it fuels citric acid cycle and fatty acid synthesis. Level of intracellular Ac-CoA fluctuates in response to changes in availability of utilizable carbon sources and metabolic activity of the cell. Since changes in intracellular concentration of Ac-CoA positively correlate with histone acetylation level, Ac-CoA might contribute to transcriptional modulation in response to nutritional stress. Moreover, Ac-CoA takes part in process of differentiation and seems to be important for cell cycle regulation. Key words: Ac-CoA, histone acetylation, nutrition, intermediary metabolism, regulation of transcription, cell cycle, glucose
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The phenomenon of mitotic catastrophe in Δcbf11 mutant
Zach, Róbert ; Převorovský, Martin (advisor) ; Rodríguez-López, María (referee)
[Eng] Fission yeast, Schizosaccharomyces pombe, represents a key model organism for studies of cell cycle regulation. Even though the biology of S. pombe is described to a great detail, certain aspects of crucial importance regarding cell cycle governing regulatory circuits are still unclear. In this study, we investigate a fission yeast CSL homologous transcription factor, Cbf11, the function of which is important for successful mitosis. Δcbf11 mutants are characterized by growth retardation and display a broad range of defects, of which we focus on catastrophic mitosis, also known as the cut (cell untimely torn) phenotype. We show the growth defects and the cut phenotype prevalence are conditional, being severe in Δcbf11 populations grown in the rich YES medium, but significantly less pronounced, when cultured in the minimal EMM medium. Our data indicate that the EMM-mediated cut phenotype rescue is caused by the excessive availability of nitrogen source (ammonium chloride in EMM), though we do not provide any molecular explanation. According to our data, mitotic defects observed in Δcbf11 mutants arise from transcriptional deregulation of lipid anabolism genes, cut6 and vht1, respectively encoding acetyl coenzyme A carboxylase and biotin transporter. Since Cut6 performance is biotin-dependent,...
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Connections between intermediary metabolism and acetylation of histones
Zach, Róbert ; Převorovský, Martin (advisor) ; Bieberstein, Nicole (referee)
Acetylation of histone proteins affects chromatin structure and functions as a coactivating signal for transcription. Acetylation of histone lysine residues is mediated by histone acetyltransferases, which utilize molecule of Ac-CoA as a donor of acetyl group. Ac-CoA is located in the centre of intermediary carbon metabolism, where it fuels citric acid cycle and fatty acid synthesis. Level of intracellular Ac-CoA fluctuates in response to changes in availability of utilizable carbon sources and metabolic activity of the cell. Since changes in intracellular concentration of Ac-CoA positively correlate with histone acetylation level, Ac-CoA might contribute to transcriptional modulation in response to nutritional stress. Moreover, Ac-CoA takes part in process of differentiation and seems to be important for cell cycle regulation. Key words: Ac-CoA, histone acetylation, nutrition, intermediary metabolism, regulation of transcription, cell cycle, glucose
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