Regulation of MLL1 H3K4 methyltransferase activity by its core components.
Histone H3 Lys4 (H3K4) methylation is a prevalent mark associated with transcription activation. A common feature of several H3K4 methyltransferase complexes is the presence of three structural components (RbBP5, Ash2L and WDR5) and a catalytic subunit containing a SET domain. Here we report the first biochemical reconstitution of a functional ... four-component mixed-lineage leukemia protein-1 (MLL1) core complex. This reconstitution, combined with in vivo assays, allows direct analysis of the contribution of each component to MLL1 enzymatic activity and their roles in transcriptional regulation. Moreover, taking clues from a crystal structure analysis, we demonstrate that WDR5 mediates interactions of the MLL1 catalytic unit both with the common structural platform and with the histone substrate. Mechanistic insights gained from this study can be generalized to the whole family of SET1-like histone methyltransferases in mammals.
Mesh Terms:
Catalytic Domain, Cell Line, DNA-Binding Proteins, Heterotrimeric GTP-Binding Proteins, Histone-Lysine N-Methyltransferase, Histones, Humans, Lysine, Methylation, Multiprotein Complexes, Myeloid-Lymphoid Leukemia Protein, Nuclear Proteins, RNA Interference, Recombinant Proteins, Transcription Factors
Catalytic Domain, Cell Line, DNA-Binding Proteins, Heterotrimeric GTP-Binding Proteins, Histone-Lysine N-Methyltransferase, Histones, Humans, Lysine, Methylation, Multiprotein Complexes, Myeloid-Lymphoid Leukemia Protein, Nuclear Proteins, RNA Interference, Recombinant Proteins, Transcription Factors
Nat. Struct. Mol. Biol.
Date: Aug. 01, 2006
PubMed ID: 16878130
View in: Pubmed Google Scholar
Download Curated Data For This Publication
106303
Switch View:
- Interactions 10