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

Journal article

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.

Authors: Dou, Y; Milne, T; Tackett, A; Smith, E; Fukuda, A

• Publication status: Published
• Journal: Cell
• Volume: 121
• Issue: 6
• Pages: 873-885
• Publication date: 2005-06-01
• DOI: 10.1016/j.cell.2005.04.031
• EISSN: 1097-4172
• ISSN: 0092-8674
• Language: English
• Keywords: Histone-Lysine N-Methyltransferase; Histone Acetyltransferases; Hela Cells; Humans; Microfilament Proteins; Myeloid-Lymphoid Leukemia Protein; Zinc Fingers; DNA-Binding Proteins; Acetyltransferases; Homeodomain Proteins; Proto-Oncogenes; Multienzyme Complexes; Transcription Factors