Abstract
BackgroundCbf11 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 FindingsUsing 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/SignificanceOur 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.
Highlights
Fission yeast, Schizosaccharomyces pombe, has been instrumental in the identification of fundamental principles of cell-cycle control [1]
We applied expression microarrays to determine which genes are potentially regulated by CSL proteins, and whether altered gene expression can explain the mutant phenotypes associated with CSL gene manipulation [22]
We analysed the transcriptomes of Δcbf11 and Δcbf12 single and double deletion mutants under various growth conditions (S4 Table), comprising rapid proliferation in rich yeast extract with supplements (YES) or minimal Edinburgh minimal medium (EMM) media, and entry into stationary phase (YES), where cells cease to proliferate
Summary
Schizosaccharomyces pombe, has been instrumental in the identification of fundamental principles of cell-cycle control [1]. Several transcription factors have been identified that regulate specific clusters of periodically expressed genes during the cell cycle [2,3,4]. These factors include the forkhead proteins Sep and Fkh, and the MADS box protein Mbx (active at M phase; role in mitosis and cytokinesis), the zinc-finger protein Ace (M/G1 phase; role in cell separation), the MBF complex and its negative regulators Nrm and Yox (G1/S phase; role in DNA replication), and the GATA-type transcription factor Ams (S phase; expression of histone genes) [5,6,7,8,9,10,11,12,13]. Cbf and Cbf, 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
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