Physical Association and Coordinate Function of the H3 K4 Methyltransferase MLL1 and the H4 K16 Acetyltransferase MOF

Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York 10021, USA.
Cell (Impact Factor: 32.24). 07/2005; 121(6):873-85. DOI: 10.1016/j.cell.2005.04.031
Source: PubMed


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.

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Available from: C. David Allis, Mar 25, 2015
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    • "Similarly, tethering a range of histone deacetylases (HDACs), including HDAC1, HDAC2, SIRT1 and SIRT2 (Hassig and Schreiber, 1997) also decreased CENP-A signals on the alphoid tetO -HAC. In contrast, tethering the H3K4 HMT MLL (also known as KMT2A) (Dou et al., 2005) increased CENP-A levels on the HAC. Previous studies have shown that H3K4me2 is required for CENP-A assembly on the alphoid tetO -HAC (Bergmann et al., 2011). "
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    • "Of note, H3K14 and H4K16 are major acetylation targets for GCN5 and MOF, respectively [32] [35] [37] [55] [60]. Additionally, MOF depletion in drosophila or human cells resulted in a genome-wide loss of H4K16Ac [32] [37] [61] [62]. In our study, we did not investigate interactions of histone demethylases with St8sia4 promoter. "
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