H3K36 Methylation Regulates Nutrient Stress Response in Saccharomyces cerevisiae by Enforcing Transcriptional Fidelity

Stephen L McDaniel; Austin J Hepperla; Jie Huang; Raghuvar Dronamraju; Alexander T Adams; Vidyadhar G Kulkarni; Ian J Davis; Brian D Strahl

doi:10.1016/j.celrep.2017.05.057

H3K36 Methylation Regulates Nutrient Stress Response in Saccharomyces cerevisiae by Enforcing Transcriptional Fidelity

Cell Rep. 2017 Jun 13;19(11):2371-2382. doi: 10.1016/j.celrep.2017.05.057.

Authors

Stephen L McDaniel¹, Austin J Hepperla², Jie Huang³, Raghuvar Dronamraju⁴, Alexander T Adams⁴, Vidyadhar G Kulkarni³, Ian J Davis⁵, Brian D Strahl⁶

Affiliations

¹ Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
² Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ Department of Statistics and Operations Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ Department of Biochemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵ Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Departments of Pediatrics and Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: ian_davis@med.unc.edu.
⁶ Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: brian_strahl@med.unc.edu.

Abstract

Set2-mediated histone methylation at H3K36 regulates diverse activities, including DNA repair, mRNA splicing, and suppression of inappropriate (cryptic) transcription. Although failure of Set2 to suppress cryptic transcription has been linked to decreased lifespan, the extent to which cryptic transcription influences other cellular functions is poorly understood. Here, we uncover a role for H3K36 methylation in the regulation of the nutrient stress response pathway. We found that the transcriptional response to nutrient stress was dysregulated in SET2-deleted (set2Δ) cells and was correlated with genome-wide bi-directional cryptic transcription that originated from within gene bodies. Antisense transcripts arising from these cryptic events extended into the promoters of the genes from which they arose and were associated with decreased sense transcription under nutrient stress conditions. These results suggest that Set2-enforced transcriptional fidelity is critical to the proper regulation of inducible and highly regulated transcription programs.

Keywords: H3K36 methylation; Set2; cryptic transcription; histone; nutrient stress; transcriptional regulation.

MeSH terms

Methylation
Protein Processing, Post-Translational / genetics*
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / metabolism*
Transcription, Genetic / genetics*

Substances

Saccharomyces cerevisiae Proteins

Abstract

MeSH terms

Substances

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