Regulation of a transcription factor network by Cdk1 coordinates late cell cycle gene expression
Article first published online: 8 APR 2014
© 2014 The Authors
The EMBO Journal
Volume 33, Issue 9, pages 1044–1060, 2 May 2014
How to Cite
The EMBO Journal (2014) 33: 1044–1060
- Issue published online: 2 MAY 2014
- Article first published online: 8 APR 2014
- Manuscript Accepted: 17 MAR 2014
- Manuscript Revised: 13 MAR 2014
- Manuscript Received: 12 SEP 2013
- National Institutes of Health. Grant Number: R00GM085013
- cell cycle;
To maintain genome stability, regulators of chromosome segregation must be expressed in coordination with mitotic events. Expression of these late cell cycle genes is regulated by cyclin-dependent kinase (Cdk1), which phosphorylates a network of conserved transcription factors (TFs). However, the effects of Cdk1 phosphorylation on many key TFs are not known. We find that elimination of Cdk1-mediated phosphorylation of four S-phase TFs decreases expression of many late cell cycle genes, delays mitotic progression, and reduces fitness in budding yeast. Blocking phosphorylation impairs degradation of all four TFs. Consequently, phosphorylation-deficient mutants of the repressors Yox1 and Yhp1 exhibit increased promoter occupancy and decreased expression of their target genes. Interestingly, although phosphorylation of the transcriptional activator Hcm1 on its N-terminus promotes its degradation, phosphorylation on its C-terminus is required for its activity, indicating that Cdk1 both activates and inhibits a single TF. We conclude that Cdk1 promotes gene expression by both activating transcriptional activators and inactivating transcriptional repressors. Furthermore, our data suggest that coordinated regulation of the TF network by Cdk1 is necessary for faithful cell division.
Cyclin-dependent kinase Cdk1 controls expression of late cell cycle genes in budding yeast, by positively and negatively regulating several key transcription factors (TFs) through phosphorylation and downstream effects on their stability and/or activity.
- Cdk1 drives the expression of late cell cycle genes by phosphorylating key transcriptional regulators.
- Phosphorylation of the repressors Yox1 and Yhp1 promotes their degradation, allowing expression of target genes to peak in M/G1 phase.
- Cdk1 exerts opposing effects on the activator Hcm1: Phosphorylation both stimulates DNA binding and promotes degradation.
- Coordinated positive and negative regulation of TFs by Cdk1 is important for cell cycle progression and optimal fitness.