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Published on: July 12, 2012
Decoupling epigenetic and genetic effects through systematic analysis of gene position
Menzies Chen1, Katherine Licon, Rei Otsuka
1Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Cell Reports
|January 8, 2013
Summary
Systematic gene deletion in yeast reveals that gene location significantly impacts expression, accounting for 35% of reporter gene activity. Specific chromatin interactions explain gene deletion resistance and inform new strain generation.
Area of Science:
- Genetics
- Epigenetics
- Molecular Biology
Background:
- Gene expression is influenced by the surrounding epigenetic landscape, as shown by classic telomere position effect studies.
- Systematic gene knockout collections offer a powerful tool to investigate position effects across the entire genome.
Purpose of the Study:
- To utilize systematic gene knockout collections to probe genome-wide position effects on gene expression.
- To quantify the contribution of chromatin environment to reporter gene activity in deleted yeast genes.
Main Methods:
- Systematic replacement of yeast genes with the kanMX marker to create knockout collections.
- Interrogation of a single reporter gene to assess chromatin environment effects.
- Analysis of histone modifications and transcriptional activator interactions.
Main Results:
- Systematic gene replacement with kanMX did not perturb the overall chromatin landscape.
- Gene position and associated chromatin differences explained 35% of kanMX reporter activity variations.
- Identified a Set2/Rpd3-mediated antagonistic interaction between histone H3 lysine 36 trimethylation and the Rap1 site in kanMX.
Conclusions:
- Chromatin influences on gene expression are locus-specific, not governed by a universal histone code.
- The identified chromatin interaction explains resistance to gene deletion and enables improved strain generation.
- Systematic gene knockout collections are valuable for dissecting chromatin-gene interactions.
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