Ji Hyun Kim1,2,*, Bo Bae Lee1,2,*, Young Mi Oh1,2, Chenchen Zhu3,4,5, Lars M. Steinmetz3,4,5, Yookyeong Lee1, Wan Kyu Kim1, Sung Bae Lee6, Stephen Buratowski7 & TaeSoo Kim1,2
1 Department of Life Science, Ewha Womans University, Seoul 03760, Korea. 2 The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 03760, Korea. 3 Genome Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. 4 Stanford Genome Technology Center, Stanford University School of Medicine, Stanford, California 94305, USA. 5 Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA. 6 Department of Brain and Cognitive Sciences, DGIST, Daegu 42988, Korea. 7 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
* These authors contributed equally to this work.
Correspondence to Stephen Buratowski or TaeSoo Kim.
H3K36 methylation by Set2 targets Rpd3S histone deacetylase to transcribed regions of mRNA genes, repressing internal cryptic promoters and slowing elongation. Here we explore the function of this pathway by analysing transcription in yeast undergoing a series of carbon source shifts. Approximately 80 mRNA genes show increased induction upon SET2 deletion. A majority of these promoters have overlapping lncRNA transcription that targets H3K36me3 and deacetylation by Rpd3S to the mRNA promoter. We previously reported a similar mechanism for H3K4me2-mediated repression via recruitment of the Set3C histone deacetylase. Here we show that the distance between an mRNA and overlapping lncRNA promoter determines whether Set2?Rpd3S or Set3C represses. This analysis also reveals many previously unreported cryptic ncRNAs induced by specific carbon sources, showing that cryptic promoters can be environmentally regulated. Therefore, in addition to repression of cryptic transcription and modulation of elongation, H3K36 methylation maintains optimal expression dynamics of many mRNAs and ncRNAs.