Regulation of MLL1 H3K4 methyltransferase activity by its core components

Yali Dou, Thomas A. Milne, Alexander J. Ruthenburg, Seunghee Lee, Jae Lee, Gregory L. Verdine, C. David Allis, Robert G. Roeder

Research output: Contribution to journalArticle

447 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)713-719
Number of pages7
JournalNature Structural and Molecular Biology
Volume13
Issue number8
DOIs
StatePublished - Aug 2006
Externally publishedYes

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Myeloid-Lymphoid Leukemia Protein
Methyltransferases
Histones
Methylation
Transcriptional Activation
Mammals
Catalytic Domain

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Dou, Y., Milne, T. A., Ruthenburg, A. J., Lee, S., Lee, J., Verdine, G. L., ... Roeder, R. G. (2006). Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nature Structural and Molecular Biology, 13(8), 713-719. https://doi.org/10.1038/nsmb1128

Regulation of MLL1 H3K4 methyltransferase activity by its core components. / Dou, Yali; Milne, Thomas A.; Ruthenburg, Alexander J.; Lee, Seunghee; Lee, Jae; Verdine, Gregory L.; Allis, C. David; Roeder, Robert G.

In: Nature Structural and Molecular Biology, Vol. 13, No. 8, 08.2006, p. 713-719.

Research output: Contribution to journalArticle

Dou, Y, Milne, TA, Ruthenburg, AJ, Lee, S, Lee, J, Verdine, GL, Allis, CD & Roeder, RG 2006, 'Regulation of MLL1 H3K4 methyltransferase activity by its core components', Nature Structural and Molecular Biology, vol. 13, no. 8, pp. 713-719. https://doi.org/10.1038/nsmb1128
Dou, Yali ; Milne, Thomas A. ; Ruthenburg, Alexander J. ; Lee, Seunghee ; Lee, Jae ; Verdine, Gregory L. ; Allis, C. David ; Roeder, Robert G. / Regulation of MLL1 H3K4 methyltransferase activity by its core components. In: Nature Structural and Molecular Biology. 2006 ; Vol. 13, No. 8. pp. 713-719.
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