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Gcn5-mediated acetylation at MBF-regulated promoters induces the G1/S transcriptional wave González Medina, Alberto, 1990- Hidalgo Hernando, Elena Ayté del Olmo, José Gene regulation Chromatin and epigenetics 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]. 2019-11-06T10:51:36Z 2019-11-06T10:51:36Z 2019 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion González-Medina A, Hidalgo E, Ayté J. Gcn5-mediated acetylation at MBF-regulated promoters induces the G1/S transcriptional wave. Nucleic Acids Res. 2019;47(16):8439-51. DOI: 10.1093/nar/gkz561 0305-1048 http://hdl.handle.net/10230/42752 http://dx.doi.org/10.1093/nar/gkz561 eng Nucleic Acids Research. 2019;47(16):8439-51 info:eu-repo/grantAgreement/ES/1PE/BFU2015-66347 info:eu-repo/grantAgreement/ES/2PE/PGC2018-097248-B-I00 info:eu-repo/grantAgreement/ES/1PE/BFU2015-71786-REDT © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf Oxford University Press