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

doi:10.1016/j.cell.2005.04.031

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

Cell. 2005 Jun 17;121(6):873-85. doi: 10.1016/j.cell.2005.04.031.

Authors

Yali Dou¹, 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

Affiliation

¹ Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York 10021, USA.

PMID: 15960975
DOI: 10.1016/j.cell.2005.04.031

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Acetyltransferases / genetics
Acetyltransferases / metabolism*
Acetyltransferases / physiology*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / physiology*
HeLa Cells
Histone Acetyltransferases
Histone-Lysine N-Methyltransferase / genetics
Histone-Lysine N-Methyltransferase / physiology*
Homeodomain Proteins / biosynthesis
Homeodomain Proteins / genetics
Humans
Microfilament Proteins / isolation & purification
Microfilament Proteins / physiology
Multienzyme Complexes / chemistry
Multienzyme Complexes / isolation & purification
Multienzyme Complexes / metabolism
Myeloid-Lymphoid Leukemia Protein
Proto-Oncogenes / genetics
Proto-Oncogenes / physiology*
Transcription Factors / genetics
Transcription Factors / physiology*
Zinc Fingers / genetics
Zinc Fingers / physiology

Substances

DNA-Binding Proteins
Homeodomain Proteins
KMT2A protein, human
Microfilament Proteins
Multienzyme Complexes
Transcription Factors
homeobox protein HOXA9
Myeloid-Lymphoid Leukemia Protein
Histone-Lysine N-Methyltransferase
Acetyltransferases
Histone Acetyltransferases
KAT8 protein, human