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.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.00256-13.

ACKNOWLEDGMENTS

We thank K. Cooper, M. Primig, A. Andrews, P. Katsamba, and M. Henry for helpful discussions and critical reading of the manuscript. We also thank S. Zhang and the Proteomics and Mass Spectrometry Core Facility at Cornell University for analysis of acetylated Ume6p.

This work was supported by Public Health Service grants GM082013 (M.J.L.) and GM086788 (R.S.) from the General Medical Institute.

We have no financial conflicts with this study.