Biology Reference
In-Depth Information
predominately involved in DNA replication. However, it should be emphasized
that there is significant functional overlap between these two transcription factor
complexes, and they do not account for all G1-S-specific transcription in this
organism (Bean
, 1997).
Much research has been done to understand how the activity of the MBF
and SBF transcription factor complexes is regulated, and this has revealed complex,
multiple levels of control. Primary control occurs through the Cdc28p/Cln3p
cyclin-dependent kinase (CDK) complex (Stuart and Wittenberg, 1995; Tyers
et al.
et al.
, 2005; Horak
et al.
, 2002; Partridge
et al.
,1993): both MBF and SBF bind to their respective promoters in early G1,
but activation of Cln3p-Cdc28p in later G1 results in the binding of the RNA
polymerase II machinery (Cosma
et al.
, 1999, 2001; Dirick
et al.
, 1995; Wijnen and
Futcher, 1999; Wijnen
,2002). The link between Cln3p and MBF/SBF is
provided by theWhi5p protein, which acts as an inhibitor of G1-S gene expression
through binding to SBF; this is reversed through its phosphorylation by Cln3p-
Cdc28p which causes it to vacate the nucleus so relieving its inhibition (Costanzo
et al.
et al.
,2004). Other proteins, with apparent activating roles for
G1-S transcription, have been identified, such as Bck2p and Stb1p (Costanzo
, 2004; de Bruin
et al.
et al.
,
2003; Ho
, 1999; Wijnen and Futcher, 1999). Another protein, Nrm1p, has
been shown to have a repressing role. The
et al.
gene is under MCB control, and
encodes a component ofMBF; as its absence results in overexpression ofMBF genes,
it acts as a repressor in a negative feedback loop inhibiting gene expression at G1-S
(de Bruin and Wittenberg, 2009; de Bruin
NRM1
,2006).
As well as these posttranslational control mechanisms, Swi4p expres-
sion is controlled at the level of transcription, being regulated through both ECB
promoter sequence motifs in its promoter resulting in gene expression at M-G1
(Section II.A.4), and through SBF- and MBF-mediated transcription at G1-S, as
part of a positive feedback loop (Foster
et al.
, 1997). MBF-
and SBF-mediated transcription is turned off in G2 through another CDK
complex containing Cdc28p-Clb1p/Clb2p, which is itself in turn activated by
transcriptional activation of
et al.
, 1993; McInerny
et al.
CLN1
and
CLN2
by MBF and SBF (Amon
et al.
,
, 1996). Yet another CDK complex, Cdc28p-
Clb6p, which is also activated transcriptionally by MBF and SBF, controls the
distribution of Swi6p in cells, causing it by direct phosphorylation to exit the
nucleus, so repressing gene expression; this event is antagonized by the phospha-
tase Cdc14p which, through dephosphorylating Swi6p, causes its nuclear entry
during G1 (Geymonat
1993; Breeden, 2000; Koch
et al.
et al.
, 2004; Sidorova
et al.
, 1995).
2. S-phase waves
The first wave of gene expression to be identified in either yeast species was the
histone gene wave in budding yeast (Hereford
, 1981, 1982). Though
potential transcription factor sites have been identified that activate this cell
et al.
