Download The Role of Gene Expression Regulation in Yeast Cell Cycle Pathway

Genome Informatics 11: 268–269 (2000)
268
The Role of Gene Expression Regulation
in Yeast Cell Cycle Pathway
Toshiaki Katayama
Minoru Kanehisa
[email protected]
[email protected]
Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011,
Japan
Keywords: cell cycle, pathway, microarray, KEGG
1
Introduction
We have constructed a cell cycle regulatory pathway of the yeast Saccharomyces cerevisiae as a knowledge base of molecular interactions (KEGG[1]/BRITE) and graphical networks (KEGG/PATHWAY).
It has been reported that about 800 genes are cell cycle-regulated in yeast according to the microarray
experiment [2], but it is not clear what fraction of the cell cycle regulatory pathway is controlled at the
level of gene expressions. Generally speaking, the cell cycle regulatory pathway consists of complex
molecular interaction networks including phosphorylation/dephosphorylation, molecular bindings, and
proteolysis, besides gene expression control. To determine the role of gene expression regulation, we
have mapped the microarray gene expression data onto our KEGG cell cycle regulatory pathway.
2
Method and Results
The KEGG cell cycle pathway map currently consists of 100 genes. In the article of Spellman’s, they
mentioned that there were 104 cell cycle regulated genes determined by traditional methods (known
regulated gene : KRG) but they could not identify 9 genes of them as cell cycle regulated by their
microarray analysis due to possible noises in their data. By using a threshold which separates 9 genes
from 104 genes in their expression data, we could divide 100 genes on our KEGG cell cycle pathway map
into 62 identifiable genes and 38 non-identifiable genes based on the changes in Spellman’s microarray
gene expression data only. Among them, 27 out of 62 genes were also identified as KRGs and 4 out
of 38 genes were also identified as non-KRGs (Table 1).
Table 1: Number of known cell cycle regulated genes on the KEGG pathway.
identified
not identified
3
3.1
KRGs
95
9
KEGG
62
38
KRGs on KEGG
27/62
4/38
Discussions
Cyclin Dependent Kinase
Cdc28 is the only cyclin dependent kinase (CDK) in yeast and its activity is regulated by cyclins
(Cln1-3, Clb1-6) depending on the cell cycle phases. So, if cyclins are transcriptionally regulated, the
CDC28 gene does not need to be regulated by gene expression. Consistently, CDC28 gene expression
could not be identified by Spellman’s gene expression data (Fig. 1).
Gene expressions on the cell cycle pathway
269
Figure 1: 38 genes in filled boxes which are not identified as cell cycle regulated according to the
microarray data.
3.2
DNA damage check point pathways
Genes which are concerned in DNA damage check point pathways such as Rad9 pathway and Rad24/Rad17
pathway seem to be silent (constant) in the expression level (Fig. 1). These genes might be expressed
in the case of DNA damage only, which may be the reason of no observed fluctuations in normal cell
cycle progression.
4
Conclusion
Many of the genes in the cell cycle regulatory pathway are shown to be transcriptionally regulated by
microarray gene expression data. However, it would be difficult to reconstruct a complete network of
molecular interactions only from the gene expression analysis. To resolve this kind of problem, it will
be necessary to use pathway data and/or two-hybrid binding data together with expression data.
5
Acknowledgements
This work was supported by grants from the Ministry of Education, Science, Sports and Culture of
Japan, the Science and Technology Agency of Japan, and the Japan Society for the Promotion of
Science. The computational resource was provided by the Supercomputer Laboratory, Institute for
Chemical Research, Kyoto University.
References
[1] Kanehisa, M. and Goto, S., KEGG: Kyoto Encyclopedia of Genes and Genomes, Nucleic Acids
Res., 28(1):27–30, 2000.
[2] Spellman, PT., Sherlock, G., Zhang, MQ., Iyer, VR., Anders, K., Eisen, MB., Brown, PO.,
Botstein, D., and Futcher, B., Comprehensive identification of cell cycle-regulated genes of the
yeast Saccharomyces cerevisiae by microarray hybridization, Mol. Biol. Cell, 9(12):3273–3297,
1998.