title: Acetylation of the transcriptional repressor Ume6p allows efficient promoter release and timely induction of the meiotic transient transcription program in yeast.
abstract: Differentiation programs require strict spatial and temporal control of gene transcription. Genes expressed during meiotic development in Saccharomyces cerevisiae display transient induction and repression. Early meiotic gene (EMG) repression during mitosis is achieved by recruiting both histone deacetylase and chromatin remodeling complexes to their promoters by the zinc cluster DNA binding protein Ume6p. Ume6p repression is relieved by ubiquitin-mediated destruction that is stimulated by Gcn5p-induced acetylation. In this report, we demonstrate that Gcn5p acetylation of separate lysines within the zinc cluster domain negatively impacts Ume6p DNA binding. Mimicking lysine acetylation using glutamine substitution mutations decreased Ume6p binding efficiency and resulted in partial derepression of Ume6p-regulated genes. Consistent with this result, molecular modeling predicted that these lysine side chains are adjacent to the DNA phosphate backbone, suggesting that acetylation inhibits Ume6p binding by electrostatic repulsion. Preventing acetylation did not impact final EMG induction levels during meiosis. However, a delay in EMG induction was observed, which became more severe in later expression classes, ultimately resulting in delayed and reduced execution of the meiotic nuclear divisions. These results indicate that Ume6p acetylation ensures the proper timing of the transient transcription program during meiotic development.
authors.affiliation: Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, New Jersey, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Law
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mallory
authors.forename: Roland L
authors.initials: RL
authors.lastname: Dunbrack
authors.forename: Randy
authors.initials: R
authors.lastname: Strich
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins; D015966:Gene Expression Regulation, Fungal / Q000235:genetics / Q000502:physiology*; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D008540:Meiosis / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C089979:UME6 protein, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor