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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.

Original publication

DOI

10.1038/nsmb1128

Type

Journal article

Journal

Nat Struct Mol Biol

Publication Date

08/2006

Volume

13

Pages

713 - 719

Keywords

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