PMID:22158900

Citation	Takahashi, YH, Westfield, GH, Oleskie, AN, Trievel, RC, Shilatifard, A and Skiniotis, G (2011) Structural analysis of the core COMPASS family of histone H3K4 methylases from yeast to human. Proc. Natl. Acad. Sci. U.S.A. 108:20526-31
Abstract	Histone H3 lysine 4 (H3K4) methylation is catalyzed by the highly evolutionarily conserved multiprotein complex known as Set1/COMPASS or MLL/COMPASS-like complexes from yeast to human, respectively. Here we have reconstituted fully functional yeast Set1/COMPASS and human MLL/COMPASS-like complex in vitro and have identified the minimum subunit composition required for histone H3K4 methylation. These subunits include the methyltransferase C-terminal SET domain of Set1/MLL, Cps60/Ash2L, Cps50/RbBP5, Cps30/WDR5, and Cps25/Dpy30, which are all common components of the COMPASS family from yeast to human. Three-dimensional (3D) cryo-EM reconstructions of the core yeast complex, combined with immunolabeling and two-dimensional (2D) EM analysis of the individual subcomplexes reveal a Y-shaped architecture with Cps50 and Cps30 localizing on the top two adjacent lobes and Cps60-Cps25 forming the base at the bottom. EM analysis of the human complex reveals a striking similarity to its yeast counterpart, suggesting a common subunit organization. The SET domain of Set1 is located at the juncture of Cps50, Cps30, and the Cps60-Cps25 module, lining the walls of a central channel that may act as the platform for catalysis and regulative processing of various degrees of H3K4 methylation. This structural arrangement suggested that COMPASS family members function as exo-methylases, which we have confirmed by in vitro and in vivo studies.
Links	PubMed PMC3251153 Online version:10.1073/pnas.1109360108
Keywords	Animals; Conserved Sequence; Cryoelectron Microscopy/methods; DNA Methylation; Histone-Lysine N-Methyltransferase/chemistry; Histone-Lysine N-Methyltransferase/genetics; Histones/chemistry; Humans; Imaging, Three-Dimensional; Insects; Methylation; Microscopy, Electron/methods; Models, Molecular; Molecular Conformation; Myeloid-Lymphoid Leukemia Protein/chemistry; Recombinant Proteins/chemistry; Saccharomyces cerevisiae/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
YEAST:SET1		GO:0044648: histone H3-K4 dimethylation	ECO:0000315:		P		Figure 4C	complete CACAO 11083
YEAST:SET1		GO:0080182: histone H3-K4 trimethylation	ECO:0000315:		P		Figure 4C	complete CACAO 11084
YEAST:SET1		GO:0042800: histone methyltransferase activity (H3-K4 specific)	ECO:0000315:		F		Figure 4C	complete CACAO 11085

References

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