An evolutionarily ‘young’ lysine residue in histone H3 attenuates transcriptional output in Saccharomyces cerevisiae
- Edel M. Hyland1,5,
- Henrik Molina2,6,
- Kunal Poorey3,
- Chunfa Jie1,
- Zhi Xie4,
- Junbiao Dai1,7,
- Jiang Qian4,
- Stefan Bekiranov3,
- David T. Auble3,
- Akhilesh Pandey2 and
- Jef D. Boeke1,8
- 1High Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
- 2Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
- 3Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22908, USA;
- 4Wilmer Bioinformatics Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Abstract
The DNA entry and exit points on the nucleosome core regulate the initial invasion of the nucleosome by factors requiring access to the underlying DNA. Here we describe in vivo consequences of eliminating a single protein–DNA interaction at this position through mutagenesis of histone H3 Lys 42 to alanine. This substitution has a dramatic effect on the Saccharomyces cerevisiae transcriptome in both the transcriptional output and landscape of mRNA species produced. We attribute this in part to decreased histone H3 occupancy at transcriptionally active loci, leading to enhanced elongation. Additionally we show that this lysine is methylated in vivo, and genetic studies of methyl-lysine mimics suggest that this modification may be crucial in attenuating gene expression. Interestingly, this site of methylation is unique to Ascomycota, suggesting a recent evolutionary innovation that highlights the evolvability of post-translational modifications of chromatin.
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Footnotes
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↵8 Corresponding author.
E-mail jboeke1{at}jhmi.edu.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.2050311.
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Supplemental material is available for this article.
- Received March 12, 2011.
- Accepted April 27, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press