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- Title
Regulation of MLL1 H3K4 methyltransferase activity by its core components.
- Authors
Yali Dou; Milne, Thomas A; Ruthenburg, Alexander J.; Seunghee Lee; Jae Woon Lee; Verdine, Gregory L.; Allis, C. David; Roeder, Robert G.
- Abstract
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.
- Subjects
HISTONES; METHYLTRANSFERASES; METHYLATION; LEUKEMIA; ENZYMATIC analysis; TRANSCRIPTION factors; GENETIC transcription
- Publication
Nature Structural & Molecular Biology, 2006, Vol 13, Issue 8, p713
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb1128