|
|
Linking transcriptional regulation of lipid metabolism with catastrophic mitosis in fission yeast
Marešová, Anna ; Převorovský, Martin (advisor) ; Čáp, Michal (referee) ; Veverka, Václav (referee)
Linking regulation of lipid metabolism with nuclear division has recently become a thoroughly investigated phenomenon. It has been shown that an undisturbed lipid metabolism is required for proper mitotic division from yeasts to mammals. In my doctoral project, I focused on the transcriptional regulation of lipid metabolism genes with respect to mitotic fidelity in the fission yeast Schizosaccharomyces pombe. Cbf11 and Mga2 are two transcriptional regulators of lipid metabolism genes. For a long time, it was assumed that they act as two independently functioning units. However, we have identified a novel regulatory partnership between Cbf11 and Mga2. Our results show that Cbf11 and Mga2 work closely together. In addition to regulating lipid metabolism, Cbf11 was known to be involved in cell cycle progression and a range of other processes. We have now determined that all known functions of Cbf11 require its canonical DNA-binding ability. Interestingly, we have identified novel roles for both Cbf11 and Mga2 and found that Mga2 mirrors the functions of Cbf11, including cell cycle control. Furthermore, we have shown that lipid metabolism has a pronounced impact on chromatin structure and the proper regulation of gene expression, and we have suggested how fatty acid synthesis contributes to mitotic...
|
|
|
Characterization of Cbf11 and Mga2 interactions in the fission yeast
Grulyová, Michaela ; Převorovský, Martin (advisor) ; Čáp, Michal (referee)
Transcription factor Cbf11 belongs to the CSL protein family. The CSL protein family is well known for its function in Notch signalling pathway, however representatives in Notch- less fission yeast were discovered. Mga2 protein is a transcription regulator of triacylglycerol and glycerophospholipid metabolism. A crosstalk between Cbf11 and Mga2 was found. Cbf11 and Mga2 share target genes, and both are required for mitotic fidelity. This thesis aims to validate and characterize relationship between these transcription regulators. We show here that protein levels of Cbf11 and Mga2 change in response to presence of the other protein, as well as in response of nitrogen source. We also determine phylogenetic distribution of Cbf11 and Mga2 among Fungi, pointing to its connection. Using proteomic analysis of mga2 and cbf11 deletion strains we found that there is an overlap between proteins up/downregulated in these strains. Together, these results acknowledge crosstalk between Cbf11 and Mga2 proteins, bringing a novel connection between CSL protein family member and a functional analogue of mammalian SREBP-1 protein Mga2.
|
|
|
Characterization of closed mitosis in the fission yeast Schizosaccharomyces pombe with perturbed lipid metabolism
Hohoš, Patrik ; Převorovský, Martin (advisor) ; Cebecauer, Marek (referee)
[EN] The division of an eukaryotic cell is mediated by the process of mitosis. It is a complex cellular process which needs to be highly regulated. In contrast to the mammalian open type of mitosis when nuclear envelope is disassembled, fission yeast Schizosaccharomyces pombe undergoes closed mitosis inside the intact nuclear compartment. Cell nucleus undergoes morphological changes as a common sphere-shaped nucleus stretches upon mitotic spindle activity forming typical dumbbell structure. Further tension results in the separation of two daughter nuclei. Such extensive changes in the nuclear envelope surface demand a sufficient supply of membrane phospholipids. Cells with perturbed lipid metabolism are unable to meet such a demand and the mitotic division in these cells usually results as a catastrophic mitotic event or CUT (Cell Untimely Torn) phenotype. Moreover, recent studies show genetic interactions between the deletions of the lipid gene regulator cbf11 and factors maintaining the centromere chromatin structure. Surprisingly, rescue of CUT phenotype has been recently reported after the deletion of several factors contributing to the centromeric H3K9 epigenetic modifications in the cells lacking the transcription factor Cbf11. Here we show no rescue of CUT phenotype after the deletion of...
|
guest ::
