Převorovský Martin, Oravcová Martina, Tvarůžková Jarmila, Zach Róbert, Folk Petr, Půta František, Bähler Jürg
Research Department of Genetics, Evolution & Environment and UCL Cancer Institute, University College London, London, United Kingdom; Department of Cell Biology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
Department of Cell Biology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
PLoS One. 2015 Sep 14;10(9):e0137820. doi: 10.1371/journal.pone.0137820. eCollection 2015.
Cbf11 and Cbf12, the fission yeast CSL transcription factors, have been implicated in the regulation of cell-cycle progression, but no specific roles have been described and their target genes have been only partially mapped.
METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of transcriptome profiling under various conditions and genome-wide analysis of CSL-DNA interactions, we identify genes regulated directly and indirectly by CSL proteins in fission yeast. We show that the expression of stress-response genes and genes that are expressed periodically during the cell cycle is deregulated upon genetic manipulation of cbf11 and/or cbf12. Accordingly, the coordination of mitosis and cytokinesis is perturbed in cells with genetically manipulated CSL protein levels, together with other specific defects in cell-cycle progression. Cbf11 activity is nutrient-dependent and Δcbf11-associated defects are mitigated by inactivation of the protein kinase A (Pka1) and stress-activated MAP kinase (Sty1p38) pathways. Furthermore, Cbf11 directly regulates a set of lipid metabolism genes and Δcbf11 cells feature a stark decrease in the number of storage lipid droplets.
CONCLUSIONS/SIGNIFICANCE: Our results provide a framework for a more detailed understanding of the role of CSL proteins in the regulation of cell-cycle progression in fission yeast.
裂殖酵母的CSL转录因子Cbf11和Cbf12与细胞周期进程的调控有关，但尚未描述其具体作用，且其靶基因仅部分被定位。
方法/主要发现：通过在各种条件下进行转录组分析以及对CSL-DNA相互作用进行全基因组分析，我们鉴定了裂殖酵母中由CSL蛋白直接和间接调控的基因。我们发现，在对cbf11和/或cbf12进行基因操作后，应激反应基因以及在细胞周期中周期性表达的基因的表达会失调。因此，在对CSL蛋白水平进行基因操作的细胞中，有丝分裂和胞质分裂的协调受到干扰，同时细胞周期进程中还存在其他特定缺陷。Cbf11的活性依赖于营养物质，蛋白激酶A（Pka1）和应激激活的丝裂原活化蛋白激酶（Sty1p38）途径的失活可减轻Δcbf11相关的缺陷。此外，Cbf11直接调控一组脂质代谢基因，Δcbf11细胞的储存脂质小滴数量显著减少。
结论/意义：我们的结果为更详细地了解CSL蛋白在裂殖酵母细胞周期进程调控中的作用提供了一个框架。
