Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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




Journal article


Nat Struct Mol Biol

Publication Date





713 - 719


Catalytic Domain, Cell Line, DNA-Binding Proteins, Heterotrimeric GTP-Binding Proteins, Histone-Lysine N-Methyltransferase, Histones, Humans, Intracellular Signaling Peptides and Proteins, Lysine, Methylation, Multiprotein Complexes, Myeloid-Lymphoid Leukemia Protein, Nuclear Proteins, RNA Interference, Recombinant Proteins, Transcription Factors