Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF

Yali Dou, Thomas A. Milne, Alan J. Tackett, Edwin R. Smith, Aya Fukuda, Joanna Wysocka, C. David Allis, Brian T. Chait, Jay L. Hess, Robert G. Roeder*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

472 Scopus citations

Abstract

A stable complex containing MLL1 and MOF has been immunoaffinity purified from a human cell line that stably expresses an epitope-tagged WDR5 subunit. Stable interactions between MLL1 and MOF were confirmed by reciprocal immunoprecipitation, cosedimentation, and cotransfection analyses, and interaction sites were mapped to MLL1 C-terminal and MOF zinc finger domains. The purified complex has a robust MLL1-mediated histone methyltransferase activity that can effect mono-, di-, and trimethylation of H3 K4 and a MOF-mediated histone acetyltransferase activity that is specific for H4 K16. Importantly, both activities are required for optimal transcription activation on a chromatin template in vitro and on an endogenous MLL1 target gene, Hox a9, in vivo. These results indicate an activator-based mechanism for joint MLL1 and MOF recruitment and targeted methylation and acetylation and provide a molecular explanation for the closely correlated distribution of H3 K4 methylation and H4 K16 acetylation on active genes.

Original languageEnglish (US)
Pages (from-to)873-885
Number of pages13
JournalCell
Volume121
Issue number6
DOIs
StatePublished - Jun 17 2005

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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