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

Abstract

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.

Spanish Ministerio de Economia y Competitividad, PLAN E, and Feder [BFU2015-66347, PGC2018-097248-B-I00]; MEIONet [BFU2015-71786-REDT]; Unidad de Excelencia Maria de Maeztu [MDM-2014-0370]; ICREA Academia Award (Generalitat de Catalunya) (to E.H.). Funding for open access charge: Spanish Ministerio de Economia y Competitividad [BFU2015-66347, PGC2018-097248-B-I00].