PT  - JOURNAL ARTICLE
AU  - Andrew M. Lerner
AU  - Austin J. Hepperla
AU  - Hashem Meriesh
AU  - Gregory R. Keele
AU  - Hayretin Yumerefendi
AU  - David Restrepo
AU  - Seth Zimmerman
AU  - James Bear
AU  - Brian Kuhlman
AU  - Ian J. Davis
AU  - Brian D. Strahl
TI  - An optogenetic switch for the Set2 methyltransferase provides evidence for rapid transcription-dependent and independent dynamics of H3K36 methylation
AID  - 10.1101/2020.03.28.013706
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.28.013706
4099  - http://biorxiv.org/content/early/2020/03/29/2020.03.28.013706.short
4100  - http://biorxiv.org/content/early/2020/03/29/2020.03.28.013706.full
AB  - Background Histone H3 lysine 36 methylation (H3K36me) is a conserved histone modification associated with transcription and DNA repair. Although the effects of H3K36 methylation have been studied, the genome-wide dynamics of H3K36me deposition and removal are not known.Results We established rapid and reversible optogenetic control for Set2, the sole H3K36 methyltransferase in yeast, by fusing the enzyme with the light activated nuclear shuttle (LANS) domain. Early H3K36me3 dynamics identified rapid methylation in vivo, with total H3K36me3 levels correlating with RNA abundance. Although genes exhibited disparate levels of H3K36 methylation, relative rates of H3K36me3 accumulation were largely linear and consistent across genes, suggesting a rate-limiting mechanism for H3K36me3 deposition. Removal of H3K36me3 was also rapid and highly dependent on the demethylase Rph1. However, the per-gene rate of H3K36me3 loss weakly correlated with RNA abundance and followed exponential decay, suggesting H3K36 demethylases act in a global, stochastic manner.Conclusion Altogether, these data provide a detailed temporal view of H3K36 methylation and demethylation that suggest transcription-dependent and independent mechanisms for H3K36me deposition and removal, respectively.