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Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes

Nature Structural & Molecular Biology volume 13, pages 852–854 (2006)Cite this article

Abstract

MLL complexes are homologs of yeast COMPASS capable of methylating histone H3 Lys4 (H3K4). ASH2L, RbBP5 and WDR5 are conserved subunits of MLL complexes with homology to the Cps40/Cps60, Cps50 and Cps30 subunits of COMPASS, respectively. We report that ASH2L differentially regulates MLL's catalysis of H3K4 trimethylation similarly to Cps40 and Cps60. Furthermore, WDR5 is required to maintain MLL complex integrity, including the stability of ASH2L within the complex. These findings offer insight into the molecular role of ASH2L, and by extension that of WDR5, in proper H3K4 trimethylation.

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Figure 1: The MLL complex, biochemical properties of its subunits and their roles in H3K4 trimethylation.
Figure 2: Effect of ASH2L reduction on H3K4 trimethylation.
Figure 3: Factors required for MLL complex stability and proper H3K4 methylation.

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Acknowledgements

The authors thank K. Wendt for editorial assistance. This work was supported by a grant from the US National Institutes of Health. A.S. is a Scholar of the Leukemia and Lymphoma Society.

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Authors and Affiliations

  1. Department of Biochemistry, Saint Louis University School of Medicine, 1402 South Grand Blvd., St. Louis, 63104, Missouri, USA

    Melissa M Steward, Jung-Shin Lee, Matt Wyatt & Ali Shilatifard

  2. Department of Pathology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Rm 7148, Charlestown, 02129, Massachusetts, USA

    Aisling O'Donovan & Bradley E Bernstein

  3. Saint Louis University Cancer Center, Saint Louis University School of Medicine, 1402 South Grand Blvd., St. Louis, 63104, Missouri, USA

    Ali Shilatifard

Authors
  1. Melissa M Steward
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  2. Jung-Shin Lee
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  5. Bradley E Bernstein
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Correspondence to Ali Shilatifard.

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Supplementary information

Supplementary Fig. 1

Reduction of ASH2L via RNAi. (PDF 413 kb)

Supplementary Methods (PDF 87 kb)

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Steward, M., Lee, JS., O'Donovan, A. et al. Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes. Nat Struct Mol Biol 13, 852–854 (2006). https://doi.org/10.1038/nsmb1131

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