Set1-dependent H3K4 methylation controls promoter proximal pause and release (TEC) of RNA polymerase II in yeast.
Antonin Morillon, Nickoletta Karabetsou, Anitha Nair, Jane Mellor
Dept of Biochemistry, Oxford university, South Parks Road, Oxford, OX13QU, UK
Covalent histone modifications are central to control gene transcription but their functional and complexity significances remain poorly understood. Here we show that different components of the complex associated with Histone Methyl-Transferase Set1 (COMPASS) determine the mono-di- or tri methylation status of H3-K4 at active genes. We present in vivo evidence that each mark has a distinct function at the transcription elongation checkpoint. Monomethylation is required for the association of Isw1 chromatin remodeling complex with chromatin. Dimethylation is the main signal allowing the transcription-dependent recruitment of the histone-chaperone Spt6 on coding region. Finally we show that trimethylation triggers transiently the association of the Histone Acetyl-Transferase Esa1 with the promoter of MET16 but not RPS11B genes suggesting a Rap1-independent recruitment mechanism for the Esa1 HAT. We present evidence showing that trimethylation controls histone H4-K8 Esa1-dependent acetylation which subsequently controls Snf2 association with the MET16 promoter. We propose a dynamic model where H3K4 monomethylation is required to pause RNAPII with highly phophorylated CTD at Ser5 whereas di and trimethylation control the release of polymerase from pausing through a combination of histone modifications and competition between Swi/Snf and Isw1 chromatin complexes.
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