Abstract
Histone acetyltransferases (HATs) assemble into multisubunit complexes in order to target distinct lysine residues on nucleosomal histones. Here, we characterize native HAT complexes assembled by the BRPF family of scaffold proteins. Their plant homeodomain (PHD)-Zn knuckle-PHD domain is essential for binding chromatin and is restricted to unmethylated H3K4, a specificity that is reversed by the associated ING subunit. Native BRPF1 complexes can contain either MOZ/MORF or HBO1 as catalytic acetyltransferase subunit. Interestingly, while the previously reported HBO1 complexes containing JADE scaffold proteins target histone H4, the HBO1-BRPF1 complex acetylates only H3 in chromatin. We mapped a small region to the N terminus of scaffold proteins responsible for histone tail selection on chromatin. Thus, alternate choice of subunits associated with HBO1 can switch its specificity between H4 and H3 tails. These results uncover a crucial new role for associated proteins within HAT complexes, previously thought to be intrinsic to the catalytic subunit.
Keywords:
BRPF1; MYST family; PHD fingers; acetyltransferase complexes; chromatin acetylation; histone tails.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Adaptor Proteins, Signal Transducing / metabolism
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Amino Acid Sequence
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Chromatin / metabolism
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DNA-Binding Proteins
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HEK293 Cells
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HeLa Cells
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Histone Acetyltransferases / chemistry
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Histone Acetyltransferases / genetics
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Histone Acetyltransferases / metabolism*
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Histones / metabolism*
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Homeodomain Proteins / metabolism
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Humans
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Methylation
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Molecular Sequence Data
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Nuclear Proteins / metabolism
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Protein Binding
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Protein Structure, Tertiary
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Protein Subunits / chemistry
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Protein Subunits / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Sequence Alignment
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Substrate Specificity
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Transcription Factors / chemistry
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Transcription Factors / metabolism
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Tumor Suppressor Proteins / chemistry
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Tumor Suppressor Proteins / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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BRPF1 protein, human
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Chromatin
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DNA-Binding Proteins
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Histones
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Homeodomain Proteins
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ING5 protein, human
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JADE1 protein, human
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Nuclear Proteins
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Protein Subunits
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Recombinant Proteins
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Transcription Factors
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Tumor Suppressor Proteins
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Histone Acetyltransferases
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KAT7 protein, human