Abstract
Methylation of histone H3 lysine 4 (H3K4) by Set1/COMPASS occurs co-transcriptionally, and is important for gene regulation. Set1/COMPASS associates with the RNA polymerase II C-terminal domain (CTD) to establish proper levels and distribution of H3K4 methylations. However, details of CTD association remain unclear. Here we report that the Set1 N-terminal region and the COMPASS subunit Swd2, which interact with each other, are both needed for efficient CTD binding in Saccharomyces cerevisiae. Moreover, a single point mutation in Swd2 that affects its interaction with Set1 also impairs COMPASS recruitment to chromatin and H3K4 methylation. A CTD interaction domain (CID) from the protein Nrd1 can partially substitute for the Set1 N-terminal region to restore CTD interactions and histone methylation. However, even when Set1/COMPASS is recruited via the Nrd1 CID, histone H2B ubiquitylation is still required for efficient H3K4 methylation, indicating that H2Bub acts after the initial recruitment of COMPASS to chromatin.
Highlights
Methylation of histone H3 lysine 4 (H3K4) by Set1/COMPASS occurs co-transcriptionally, and is important for gene regulation
N-terminal deletion of Set[1] (SΔ200) attenuated Set[1] association with Ser5P–C-terminal domain (CTD) and total RNA polymerase II (RNApII). This result suggests that the N-terminal domain of Set[1] that interacts with Swd[2] is important for the direct or indirect association of Set[1] with RNApII
We have previously shown that trimethylation occurs over multiple rounds of transcription[35], so in mutants with reduced COMPASS occupancy or activity, promoter–proximal nucleosomes maximally attain H3K4me[2], while downstream nucleosomes that would normally have H3K4me[2] only reach H3K4me[1], making it appear that the H3K4 methylation gradient has shifted upstream[35]
Summary
Methylation of histone H3 lysine 4 (H3K4) by Set1/COMPASS occurs co-transcriptionally, and is important for gene regulation. Set1/COMPASS associates with the RNA polymerase II C-terminal domain (CTD) to establish proper levels and distribution of H3K4 methylations. A CTD interaction domain (CID) from the protein Nrd[1] can partially substitute for the Set[1] N-terminal region to restore CTD interactions and histone methylation. Deletion or depletion of individual COMPASS subunits differentially impairs Set[1] stability and the pattern of H3K4 methylation along active genes[12,14,22,23,24]. Relevant to this study, depletion of the WD40 repeat protein
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