Gcn5-mediated acetylation at MBF-regulated promoters induces the G1/S transcriptional wave

• Published in: Nucleic acids research Vol. 47; no. 16; pp. 8439 - 8451
• Main Authors: González-Medina, Alberto, Hidalgo, Elena, Ayté, José
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 19.09.2019
• Subjects: Acetylation; Acetyltransferases - genetics; Acetyltransferases - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromatin - chemistry; Chromatin - metabolism; Chromatin and epigenetics; Feedback, Physiological; G1 Phase Cell Cycle Checkpoints - genetics; Gene Expression Regulation, Fungal; Gene regulation; Gene regulation, Chromatin and Epigenetics; Histones - genetics; Histones - metabolism; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Promoter Regions, Genetic; Protein Binding; Repressor Proteins - genetics; Repressor Proteins - metabolism; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; Time Factors; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/gkz561

In fission yeast, MBF-dependent transcription is inactivated at the end of S phase through a negative feedback loop that involves the co-repressors, Yox1 and Nrm1. Although this repression system is well known, the molecular mechanisms involved in MBF activation remain largely unknown. Compacted chromatin constitutes a barrier to activators accessing promoters. Here, we show that chromatin regulation plays a key role in activating MBF-dependent transcription. Gcn5, a part of the SAGA complex, binds to MBF-regulated promoters through the MBF co-activator Rep2 in a cell cycle-dependent manner and in a reverse correlation to the binding of the MBF co-repressors, Nrm1 or Yox1. We propose that the co-repressors function as physical barriers to SAGA recruitment onto MBF promoters. We also show that Gcn5 acetylates specific lysine residues on histone H3 in a cell cycle-regulated manner. Furthermore, either in a gcn5 mutant or in a strain in which histone H3 is kept in an unacetylated form, MBF-dependent transcription is downregulated. In summary, Gcn5 is required for the full activation and correct timing of MBF-regulated gene transcription.