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

Publication date: 13 June 2017
Source:Cell Reports, Volume 19, Issue 11
Author(s): Stephen L. McDaniel, Austin J. Hepperla, Jie Huang, Raghuvar Dronamraju, Alexander T. Adams, Vidyadhar G. Kulkarni, Ian J. Davis, Brian D. Strahl
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.

Graphical abstract

Teaser

McDaniel et al. find that Set2-mediated H3K36 methylation is necessary for proper TOR signaling and the nutrient stress response. Cells lacking Set2 display a disrupted transcriptional response to nutrient stress that is correlated with increased intragenic bi-directional transcription within genes that interferes with proper transcription.


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