Correlating Transcription and Cell Cycle

Source: Klevecz, R.R., Bolen, J., Forrest, G., and Murray, D.B. A genomewide oscillation in transcription gates DNA replication and cell cycle. 2004. PNAS, 101(5): 1200-5

The authors measured transcript abundance as it fluctuated with changes in dissolved oxygen content for yeast. They found that there were three timepoints were gene expression peaked: two peaks with >2,000 genes reaching their maximum expression when oxygen levels were high (cells nonrespiring) and one peak where 650 genes reached their maximum expression when oxygen levels were low (cells respiring). Compared transcripts to states, and found that mitochondrial genes are expressed during reductive phase when mitochondrial function is minimal; while sulfur metabolism genes are expressed in respiratory phase right before they are needed for DNA replication in beginning of reductive phase. Most periods were ~40 minutes, and other studies showed that on a variety of media the doubling times of yeast were some multiple of 40 minutes.



•Other notes:
-cell-to-cell synchronization involved through respiratory inhibition by H2S and phase shifts due to acetaldehyde
-87% of genes expressed maximally in reductive phase
=2400 early, 2200 late
-650 genes maximum expression in oxidative phase
-4-12 minute lag between transcript peak and maximum gene product function
-DNA replication begins abruptly at end of respiration, H2S levels rise
-separation in time between oxidative and reductive phases goes to transcript levels and is coordinated with DNA replication
=prevents oxidative stress