H3 lysine 4 di- and tri-methylation deposited by cryptic transcription attenuates promoter activation

Abstract

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. There is a Have you seen ...? (June 2009) associated with this Article.