Linke, ChristianChasapi, AnastasiaGonzález Novo, AlbertoAl-Sawad, IstabrakTognetti, SilviaKlipp, E., 1965-Loog, MartKrobitsch, SylviaPosas Garriga, FrancescXenarios, IoannisBarberis, Matteo2018-11-122018-11-122017Linke C, Chasapi A, González-Novo A, Al Sawad I, Tognetti S, Klipp E et al. A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle. NPJ Syst Biol Appl. 2017 Mar 6; 3: 7. DOI: 10.1038/s41540-017-0008-12056-7189http://hdl.handle.net/10230/35731Precise timing of cell division is achieved by coupling waves of cyclin-dependent kinase (Cdk) activity with a transcriptional oscillator throughout cell cycle progression. Although details of transcription of cyclin genes are known, it is unclear which is the transcriptional cascade that modulates their expression in a timely fashion. Here, we demonstrate that a Clb/Cdk1-mediated regulation of the Fkh2 transcription factor synchronizes the temporal mitotic CLB expression in budding yeast. A simplified kinetic model of the cyclin/Cdk network predicts a linear cascade where a Clb/Cdk1-mediated regulation of an activator molecule drives CLB3 and CLB2 expression. Experimental validation highlights Fkh2 as modulator of CLB3 transcript levels, besides its role in regulating CLB2 expression. A Boolean model based on the minimal number of interactions needed to capture the information flow of the Clb/Cdk1 network supports the role of an activator molecule in the sequential activation, and oscillatory behavior, of mitotic Clb cyclins. This work illustrates how transcription and phosphorylation networks can be coupled by a Clb/Cdk1-mediated regulation that synchronizes them.application/pdfeng© Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the materialCicle cel·lularinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41540-017-0008-1info:eu-repo/semantics/openAccess