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

作者：Pinskaya Marina; Gourvennec Stephanie; Morillon Antonin^*

来源：The EMBO Journal, 2009, 28(12): 1697-1707.

DOI：10.1038/emboj.2009.108

• chromatin
• CUT
• regulatory RNA
• Set1
• transcription

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. The EMBO Journal (2009) 28, 1697-1707. doi:10.1038/emboj.2009.108; Published online 30 April 2009

• 出版日期2009-6-17