PMID:24402317

Citation	Thornton, JL, Westfield, GH, Takahashi, YH, Cook, M, Gao, X, Woodfin, AR, Lee, JS, Morgan, MA, Jackson, J, Smith, ER, Couture, JF, Skiniotis, G and Shilatifard, A (2014) Context dependency of Set1/COMPASS-mediated histone H3 Lys4 trimethylation. Genes Dev. 28:115-20
Abstract	The stimulation of trimethylation of histone H3 Lys4 (H3K4) by H2B monoubiquitination (H2Bub) has been widely studied, with multiple mechanisms having been proposed for this form of histone cross-talk. Cps35/Swd2 within COMPASS (complex of proteins associated with Set1) is considered to bridge these different processes. However, a truncated form of Set1 (762-Set1) is reported to function in H3K4 trimethylation (H3K4me3) without interacting with Cps35/Swd2, and such cross-talk is attributed to the n-SET domain of Set1 and its interaction with the Cps40/Spp1 subunit of COMPASS. Here, we used biochemical, structural, in vivo, and chromatin immunoprecipitation (ChIP) sequencing (ChIP-seq) approaches to demonstrate that Cps40/Spp1 and the n-SET domain of Set1 are required for the stability of Set1 and not the cross-talk. Furthermore, the apparent wild-type levels of H3K4me3 in the 762-Set1 strain are due to the rogue methylase activity of this mutant, resulting in the mislocalization of H3K4me3 from the promoter-proximal regions to the gene bodies and intergenic regions. We also performed detailed screens and identified yeast strains lacking H2Bub but containing intact H2Bub enzymes that have normal levels of H3K4me3, suggesting that monoubiquitination may not directly stimulate COMPASS but rather works in the context of the PAF and Rad6/Bre1 complexes. Our study demonstrates that the monoubiquitination machinery and Cps35/Swd2 function to focus COMPASS's H3K4me3 activity at promoter-proximal regions in a context-dependent manner.
Links	PubMed PMC3909785 Online version:10.1101/gad.232215.113
Keywords	Histone-Lysine N-Methyltransferase/metabolism; Histones/metabolism; Lysine/metabolism; Membrane Proteins/metabolism; Methylation; Phosphoric Monoester Hydrolases/metabolism; Protein Stability; Saccharomyces cerevisiae/enzymology; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
YEAST:SET1	involved_in	GO:0044648: histone H3-K4 dimethylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
YEAST:SET1	involved_in	GO:0080182: histone H3-K4 trimethylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
YEAST:SET1		GO:0080182: histone H3-K4 trimethylation	ECO:0000315:		P		Figure 1B and Figure 3A both show wild type SET1 (labeled as FL Set1 for "Full-length Set1"), is involved in H3K4 trimethylation.	complete CACAO 10432
YEAST:SET1		GO:0044648: histone H3-K4 dimethylation	ECO:0000315:		P		Both Figure 1B and Figure 3A show Set1 (labeled as FL set1 for "Full length Set1") is involved in dimethylation.	complete CACAO 10433

References

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