Biology Reference
In-Depth Information
Mcm1p is fascinating and unique in cell cycle regulated transcription in
that it is involved in at least two waves of gene expression at different times of
the cell cycle (and indeed other important transcription control mechanisms).
As already described, these differences are conferred by ancillary transcription
factors that bind alongside Mcm1p on promoters with, in the case of M-G1 gene
expression, these being two homeodomain proteins, Yox1p and Yhp1p. Here,
Mcm1p binds to a promoter element named an early cell cycle box (ECB) in the
promoters of important cell cycle genes such as
, themselves rate
limiting for cell cycle progression, and essential for the control of subsequent
waves of gene expression at G1-S (MacKay
SWI4
and
CLN3
, 1997).
Regulated expression is not conferred through changes in Mcm1p binding to
DNA, as it is in contact with promoters throughout the cell cycle (Mai
et al.
, 2001; McInerny
et al.
,
2002), instead through changes in binding of Yox1p and Yhp1p, with their
removal from promoters allowing gene expression at M-G1 (Pramila
et al.
et al.
,
2002). As
is itself under transcriptional regulation by SBF, and Mcm1p
controls the expression of
YOX1
SWI4
encoding a component of SBF, this sets up a
negative feedback loop.
A separate wave of gene expression at M-G1 is controlled by the
paralogous pair of transcription factors, Swi5p and Ace2p, with these two having
overlapping, but distinct, roles in these processes, reminiscent of SBF/MBF at
G1-S (Dohrmann
et al.
, 1992, 1996; Doolin
et al.
, 2001; Laabs
et al.
, 2003;
McBride
, 1999). Both transcription factors bind to the same promoter
sequence, which has been called a Swi5-binding site and is present in a number
of gene promoters for genes that encode products required for cytokinesis and cell
separation.
In a crucial linking mechanism between two waves of gene expression,
et al.
the
genes are transcriptionally regulated by the Mcm1p-Fkh2p
system at G2-M. Swi5p protein is also negatively regulated by Clb2p-Cdc28p,
as the specific degradation of Clb2p during anaphase results in the dephosphory-
lation of Swi5p, so causing its retention in the nucleus and allowing it to activate
target genes (Moll
ACE2
and
SWI5
, 1990). In contrast, phosphorylation
of Ace2p by the RAM network causes its activation to stimulate gene expression
(Nelson
et al.
, 1991; Nasmyth
et al.
, 2003).
Swi5p and Ace2p also have other important roles in cell cycle gene
expression, being part of the process which controls mother-daughter cell
identity. This occurs through the accumulation of the product of one of their
target genes,
et al.
: Ash1p, along with Ace2p, accumulates only in daughter
cells, thus ensuring the specific control of gene expression in this cell type
(Bertrand
ASH1
et al.
, 1998; Bobola
et al.
, 1996; Cosma, 2004; McBride
et al.
, 1999;
Paquin and Chartrand, 2008; Shen
, 2009; Sil and Herskowitz, 1996).
Another essential function for Swi5p is the control of mating-type switching
through the control of the
et al.
endonuclease, which is also mediated by SBF
(Andrews and Herskowitz, 1989a; Breeden and Nasmyth, 1987).
HO
