H3 lysine 4 di- and tri-methylation deposited by cryptic transcription attenuates promoter activation.
Set1-dependent H3K4 di- and tri-methylation (H3K4me2/3) have been associated with active transcription. Recent data indicate that the H3K4me2/3 also plays a poorly characterized RNA-dependent repressive role. Here, we show that GAL1 promoter is attenuated by the H3K4me2/3 deposited by cryptic transcription. The H3K4me2/3 delay the recruitment of RNA polymerase II (RNAPII) and TBP on GAL1 promoter. Inactivation of RNA decay components revealed the existence of the RNAPII-dependent unstable RNAs, initiating upstream of GAL1 (GAL1ucut). GAL1ucut RNAs are synthesized in glucose and require the Reb1 transcription factor. Consistent with a regulatory function of the cryptic transcription, Reb1 depletion leads to a decrease of H3K4me3 on GAL10-GAL1 locus in glucose and to an acceleration of GAL1 induction. A candidate approach shows that the RPD3 histone deacetylase attenuates GAL1 induction and is tethered at the GAL10-GAL1 locus by H3K4me2/3 upon repression. Strikingly, Set1-dependent Rpd3 recruitment represses also the usage of a hidden promoter within SUC2, suggesting a general function for H3K4me2/3 in promoter fidelity. Our data support a model wherein certain promoters are embedded in a repressive chromatin controlled by cryptic transcription.
Pinskaya
Marina
M
Centre de Génétique Moléculaire CNRS, Université Pierre et Marie Curie, Gif sur Yvette, France.
Gourvennec
Stéphanie
S
Morillon
Antonin
A
D003593:Cytoplasm / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
D006657:Histones; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D012319:RNA Polymerase II; D006655:Histone Deacetylases; D008239:Lysine