title: Histone H3K27 trimethylation inhibits H3 binding and function of SET1-like H3K4 methyltransferase complexes.
abstract: Trimethylated histone H3 lysine 4 (H3K4) and H3K27 generally mark transcriptionally active and repressive chromatins, respectively. In most cell types, these two modifications are mutually exclusive, and this segregation is crucial for the regulation of gene expression. However, how this anticorrelation is achieved has not been fully understood. Here, we show that removal of the H3K27 trimethyl mark facilitates recruitment of SET1-like H3K4 methyltransferase complexes to their target genes by eliciting a novel interaction between histone H3 and two common subunits, WDR5 and RBBP5, of SET1-like complexes. Consistent with this result, H3K27 trimethylation destabilizes interactions of H3 with SET1-like complexes and antagonizes their ability to carry out H3K4 trimethylation of peptide (H3 residues 1 to 36), histone octamer, and mononucleosome substrates. Altogether, our studies reveal that H3K27 trimethylation of histone H3 represses a previously unrecognized interaction between H3 and SET1-like complexes. This provides an important mechanism that directs the anticorrelation between H3K4 and H3K27 trimethylation.
authors.affiliation: Neuroscience Section, Papé Family Pediatric Research Institute.
authors.forename: Dae-Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Zhanyun
authors.initials: Z
authors.lastname: Tang
authors.forename: Miho
authors.initials: M
authors.lastname: Shimada
authors.forename: Beat
authors.initials: B
authors.lastname: Fierz
authors.forename: Brian
authors.initials: B
authors.lastname: Houck-Loomis
authors.forename: Maya
authors.initials: M
authors.lastname: Bar-Dagen
authors.forename: Seunghee
authors.initials: S
authors.lastname: Lee
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Tom W
authors.initials: TW
authors.lastname: Muir
authors.forename: Robert G
authors.initials: RG
authors.lastname: Roeder
authors.forename: Jae W
authors.initials: JW
authors.lastname: Lee
mesh_terms: D001665:Binding Sites; D002470:Cell Survival; D004268:DNA-Binding Proteins; D044127:Epigenesis, Genetic; D057809:HEK293 Cells; D006367:HeLa Cells; D056466:Histone Demethylases / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008745:Methylation; D009097:Multienzyme Complexes / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D015533:Transcriptional Activation; D014212:Tretinoin / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; C470552:RBBP5 protein, human; C502547:WDR5 protein, human; D014212:Tretinoin; D056466:Histone Demethylases; C523998:KDM6A protein, human; D011495:Histone-Lysine N-Methyltransferase; C526068:Setd1A protein, human