Evidence suggests that a semi-autonomous transcriptional network acts in concert with the CDK-cyclin machinery
to regulate the cell cycle. Several gene expression studies in
Saccharomyces cerevisiae have identified approximately 800 to 1200 genes
that change expression over the course of the cell cycle. They are
transcribed at high levels at specific points in the cell cycle, and
remain at lower levels throughout the rest of the cell cycle. While the
set of identified genes differs between studies due to the computational
methods and criterion used to identify them, each study indicates that a
large portion of yeast genes are temporally regulated.
Many periodically expressed genes are driven by transcription factors
that are also periodically expressed. One screen of single-gene
knockouts identified 48 transcription factors (about 20% of all
non-essential transcription factors) that show cell cycle progression
defects. Genome-wide studies using high throughput technologies have
identified the transcription factors that bind to the promoters of yeast
genes, and correlating these findings with temporal expression patterns
have allowed the identification of transcription factors that drive
phase-specific gene expression. The expression profiles of these
transcription factors are driven by the transcription factors that peak
in the prior phase, and computational models have shown that a
CDK-autonomous network of these transcription factors is sufficient to
produce steady-state oscillations in gene expression).
Experimental evidence also suggests that gene expression can oscillate with the period seen in dividing wild-type cells independently of the CDK machinery.
Orlando et al. used microarrays to measure the expression of a set of
1,271 genes that they identified as periodic in both wild type cells and
cells lacking all S-phase and mitotic cyclins (clb1,2,3,4,5,6). Of the
1,271 genes assayed, 882 continued to be expressed in the
cyclin-deficient cells at the same time as in the wild type cells,
despite the fact that the cyclin-deficient cells arrest at the border
between G1 and S phase. However, 833 of the genes assayed changed
behavior between the wild type and mutant cells, indicating that these
genes are likely directly or indirectly regulated by the CDK-cyclin
machinery. Some genes that continued to be expressed on time in the
mutant cells were also expressed at different levels in the mutant and
wild type cells. These findings suggest that while the transcriptional
network may oscillate independently of the CDK-cyclin oscillator, they
are coupled in a manner that requires both to ensure the proper timing
of cell cycle events. Other work indicates that phosphorylation, a
post-translational modification, of cell cycle transcription factors by
Cdk1 may alter the localization or activity of the transcription factors
in order to tightly control timing of target genes (Ubersax et al.
2003; Sidorova et al. 1995; White et al. 2009).
While oscillatory transcription plays a key role in the progression of the yeast cell cycle, the CDK-cyclin machinery operates independently in the early embryonic cell cycle.
Before the midblastula transition, zygotic transcription does not occur
and all needed proteins, such as the B-type cyclins, are translated
from maternally loaded mRNA.
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