Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF.
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.
Mesh Terms:
Acetyltransferases, DNA-Binding Proteins, Hela Cells, Histone Acetyltransferases, Histone-Lysine N-Methyltransferase, Homeodomain Proteins, Humans, Microfilament Proteins, Multienzyme Complexes, Myeloid-Lymphoid Leukemia Protein, Proto-Oncogenes, Transcription Factors, Zinc Fingers
Acetyltransferases, DNA-Binding Proteins, Hela Cells, Histone Acetyltransferases, Histone-Lysine N-Methyltransferase, Homeodomain Proteins, Humans, Microfilament Proteins, Multienzyme Complexes, Myeloid-Lymphoid Leukemia Protein, Proto-Oncogenes, Transcription Factors, Zinc Fingers
Cell
Date: Jun. 17, 2005
PubMed ID: 15960975
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