Cell Cycle Regulated Gene Expression in Yeasts - Advances in Genetics - page 64

Most encode products required for processes at the end of the cell cycle, such as
chromosome separation, cytokinesis, and septation. The promoter sequences and
transcription factors required for their expression have been identified, named
pombe cell cycle boxes (PCBs) and PCB-binding factor (PBF), respectively
(Anderson

, 2002). At least three components of PBF have been identified,
and these include two forkhead-like transcription factors, Fkh2p and Sep1p, and
a MADS box-like protein, Mbx1p (Buck

et al.

et al. , 2004; Bulmer et al. , 2004; Szilagyi

et al. , 2000).

The two forkhead transcription factors have complementary and oppos-
ing roles in regulating gene expression: Fkh2p, which is only bound to PCB
promoters when M-G1 genes are not being expressed, appears to have a repres-
sive role; in contrast, Sep1p is only bound when genes are being expressed, and
thus has a positive role (Papadopoulou

, 2005; Zilahi et al.

, 2008). These proposed functions are
supported by experiments where either gene has been deleted from the chromo-
some in cells, with the absence of Fkh2p resulting is unnaturally high transcrip-
tion of M-G1 genes and, in contrast, the absence of Sep1p resulting in low gene
expression (Buck

et al.

, 2004). Thus, the
stepwise replacement of one forkhead transcription factor by another appears to
be a crucial part of the control process. How this change in binding is mediated is
not yet understood, although Fkh2p and Sep1p bind to each other in cells,
suggesting that a transient interaction between the two may be part of the
process, and Sep1p is

et al. , 2004; Bulmer et al. , 2004; Rustici et al.

required for Fkh2p function (Buck et al. , 2004;

Papadopoulou , 2008). Fkh2p also binds to its own promoter and is periodi-

cally expressed as part of the cluster at M-G1, so forming a negative feedback
loop. Furthermore, both proteins are phosphorylated by as yet unknown protein
kinases, although genetic experiments imply a role for Cdc2p with Sep1p
(Grallert

et al.

, 1998).
Another level of control of M-G1 gene expression occurs through
Mbx1p. This, too, is a cell cycle regulated phosphoprotein, but in this case the
protein kinase has been identified as being Plo1p, a polo-like kinase
(Papadopoulou

et al.

, 2008). Plo1p phosphorylates Mbx1p at M-G1, with this
occurring in part through Plo1p only binding to PCB promoters at this cell cycle
time. As the

et al.

plo1 þ gene itself is expressed at M-G1 and has PCB sequences in its
promoter, Plo1p acts

in a positive feedback loop controlling its own

transcription.
Similar to the situation in budding yeast, a group of genes whose
function is required for cell separation is controlled by an Ace2p transcription
factor (Alonso-Nunez

, 2005). This group, which includes
eng1 þ , encoding Eng1p, which controls degradation of the cell septum, is also
expressed at M-G1 under the control of an ACE2 promoter motif (Dekker

et al. , 2005; Petit et al.

et al. ,

2006; Mart´n-Cuadrado , 2003). Ace2p is itself regulated by PBF, so these

two transcription waves are functionally linked (Rustici

et al.

et al. , 2004).