Abstract
The methylation of histone 3 lysine 4 (H3K4) is carried out by an evolutionarily conserved family of methyltransferases referred to as complex of proteins associated with Set1 (COMPASS). The activity of the catalytic SET domain (su(var)3-9, enhancer-of-zeste, and trithorax) is endowed through forming a complex with a set of core proteins that are widely shared from yeast to humans. We obtained cryo-electron microscopy (cryo-EM) maps of the yeast Set1/COMPASS core complex at overall 4.0- to 4.4-Å resolution, providing insights into its structural organization and conformational dynamics. The Cps50 C-terminal tail weaves within the complex to provide a central scaffold for assembly. The SET domain, snugly positioned at the junction of the Y-shaped complex, is extensively contacted by Cps60 (Bre2), Cps50 (Swd1), and Cps30 (Swd3). The mobile SET-I motif of the SET domain is engaged by Cps30, explaining its key role in COMPASS catalytic activity toward higher H3K4 methylation states. The cryo-EM structure of a fully functional COMPASS complex reveals the intricate structural coordination of the methyltransferase subunit by its partner proteins.
Original language | English (US) |
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Pages (from-to) | 1117-1126.e12 |
Journal | Cell |
Volume | 174 |
Issue number | 5 |
DOIs | |
State | Published - Aug 23 2018 |
Funding
This work was supported by NIH grant DK090165 (G.S.), an Outstanding Investigator Award R35CA197569 from the National Cancer Institute (A.S.), and a CIHR grant (J.-F.C.).
Keywords
- COMPASS
- MLL
- cryo-EM
- epigenetics
- histone methylation
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
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Dive into the research topics of 'Structure and Conformational Dynamics of a COMPASS Histone H3K4 Methyltransferase Complex'. Together they form a unique fingerprint.Datasets
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Crystal structure of Myceliophteria_thermophila Cps50 (Swd1) beta-propeller domain
Qu, Q. (Contributor), Takahashi, Y.-H. (Contributor), Yang, Y. (Contributor), Hu, H. (Contributor), Zhang, Y. (Contributor), Brunzelle, J. S. (Contributor), Couture, J.-F. (Contributor), Shilatifard, A. (Contributor) & Skiniotis, G. (Contributor), Protein Data Bank (PDB), Jul 25 2018
DOI: 10.2210/pdb6E29/pdb, https://www.wwpdb.org/pdb?id=pdb_00006e29
Dataset
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Structure of histone H3k4 methyltransferase
Qu, Q. (Contributor), Takahashi, Y.-H. (Contributor), Yang, Y. (Contributor), Hu, H. (Contributor), Zhang, Y. (Contributor), Brunzelle, J. S. (Contributor), Couture, J.-F. (Contributor), Shilatifard, A. (Contributor) & Skiniotis, G. (Contributor), Protein Data Bank (PDB), Sep 5 2018
DOI: 10.2210/pdb6BX3/pdb, https://www.wwpdb.org/pdb?id=pdb_00006bx3
Dataset