Fkh2p and Sep1p regulate mitotic gene transcription in fission yeast

Abstract

In the fission yeast Schizosaccharomyces pombe, several genes including cdc15+, spo12+, fin1+, slp1+, ace2+ and plo1+ are periodically expressed during M phase. The products of these genes control various aspects of cell cycle progression including sister chromatid separation, septation and cytokinesis. We demonstrate that periodic expression of these genes is regulated by a common promoter sequence element, named a PCB. In a genetic screen for cell cycle regulators we have identified a novel forkhead transcription factor, Fkh2p, which is periodically phosphorylated in M phase. We show that Fhk2p and another forkhead transcription factor, Sep1p, are necessary for PCB-driven M-phase-specific transcription. In a previous report we identified a complex by electrophoretic mobility shift assay, which we termed PBF, that binds to a 150 bp region of the cdc15+ promoter that contains the PCB element. We have identified Mbx1p, a novel MADS box protein, as a component of PBF. However, although Mbx1p is periodically phosphorylated in M phase, Mbx1p is not required for periodic gene transcription in M phase. Moreover, although PBF is absent in strains bearing a C-terminal epitope tag on Fkh2p, simultaneous deletion of fkh2+ and sep1+ does not abolish PBF binding activity. This suggests that Mbx1p binds to gene promoters, but is not required for transcriptional activation. Together these results suggest that the activation of the Fkh2p and Sep1p forkhead transcription factors triggers mitotic gene transcription in fission yeast.

Ace2p Controls the Expression of Genes Required for Cell Separation inSchizosaccharomyces pombe

“…We have shown that deletion of the five repeats eliminated ace2 ϩ transcription and function, indicating that they are important for ace2 ϩ expression. Interestingly, two of these sites (at Ϫ375 base pairs and Ϫ220 base pairs) are located 8 and 15 nt downstream of the GCAAC G / A sequence (the PCB element), which is the binding site for the MADS box protein Mbx1p (Buck et al, 2004). These authors have proposed that Mbx1p might form a complex with Sep1p and a second forkhead-like factor, Fkh2p, to control periodic gene transcription in M phase.…”

Promoter-driven splicing regulation in fission yeast

“…It is involved in septum formation, cytokinesis, nuclear structure and mitotic spindle function (Bulmer et al, 2004). It was also suggested that Fkh2 was implicated in the periodic gene expression of M and G1 phases (Buck et al, 2004), (when it is phosphorylated (Buck et al, 2004)) by negatively regulating the transcription of a cluster of genes (Rustici et al, 2004). The null mutant displays longer length, coldsensitive, heat-sensitive and slow-growing phenotypes (Buck et al, 2004), (Bulmer et al, 2004).…”

“…It was also suggested that Fkh2 was implicated in the periodic gene expression of M and G1 phases (Buck et al, 2004), (when it is phosphorylated (Buck et al, 2004)) by negatively regulating the transcription of a cluster of genes (Rustici et al, 2004). The null mutant displays longer length, coldsensitive, heat-sensitive and slow-growing phenotypes (Buck et al, 2004), (Bulmer et al, 2004). Regarding meiosis, a null mutant presents low levels of ste11 mRNA, dephosphorylation at Fkh2 residues T314 and S462 is required for binding to ste11 promoter region and induction of ste11 transcription during nitrogen starvation (Shimada et al, 2007).…”

Regulation of gene expression during M-G1-phase in fission yeast through Plo1p and forkhead transcription factors

“…As in budding (Zilahi et al, 2000;Buck et al, 2004;Bulmer et al, 2004). Two of these, Fkh2p and Mbx1p, are phosphoproteins, whose phosphorylation status varies through the cell cycle peaking in late M-phase, with genetic experiments implying a role for the Polo protein kinase Plo1p (Anderson et al, 2002;Buck et al, 2004;Bulmer et al, 2004). In this paper we examine how this transcription factor complex is regulated, and reveal a role for phosphorylation of Mbx1p by Plo1p, together with cell-cyclespecific binding by Fkh2p, Sep1p and Plo1p to PCB promoters.…”

“…The products of these genes regulate spindle formation, the onset of anaphase, the formation and placement of the actomyosin ring and cytokinesis. As in budding (Zilahi et al, 2000;Buck et al, 2004;Bulmer et al, 2004). Two of these, Fkh2p and Mbx1p, are phosphoproteins, whose phosphorylation status varies through the cell cycle peaking in late M-phase, with genetic experiments implying a role for the Polo protein kinase Plo1p (Anderson et al, 2002;Buck et al, 2004;Bulmer et al, 2004).…”