title: Commitment to a cellular transition precedes genome-wide transcriptional change.
abstract: In budding yeast, commitment to cell division corresponds to activating the positive feedback loop of G1 cyclins controlled by the transcription factors SBF and MBF. This pair of transcription factors has over 200 targets, implying that cell-cycle commitment coincides with genome-wide changes in transcription. Here, we find that genes within this regulon have a well-defined distribution of transcriptional activation times. Combinatorial use of SBF and MBF results in a logical OR function for gene expression and partially explains activation timing. Activation of G1 cyclin expression precedes the activation of the bulk of the G1/S regulon, ensuring that commitment to cell division occurs before large-scale changes in transcription. Furthermore, we find similar positive feedback-first regulation in the yeasts S. bayanus and S. cerevisiae, as well as human cells. The widespread use of the feedback-first motif in eukaryotic cell-cycle control, implemented by nonorthologous proteins, suggests its frequent deployment at cellular transitions.
authors.affiliation: Department of Applied Physics, Stanford University, Stanford CA 94305, USA.
authors.forename: Umut
authors.initials: U
authors.lastname: Eser
authors.forename: Melody
authors.initials: M
authors.lastname: Falleur-Fettig
authors.forename: Amy
authors.initials: A
authors.lastname: Johnson
authors.forename: Jan M
authors.initials: JM
authors.lastname: Skotheim
mesh_terms: D002455:Cell Division; D050684:E2F Transcription Factors / Q000378:metabolism / Q000502:physiology; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D018085:Regulon / Q000502:physiology; D012440:Saccharomyces / Q000166:cytology / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: D050684:E2F Transcription Factors; C083209:MBP1 protein, S cerevisiae; C081540:SBF protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors