Abstract
CFP1 is a CXXC domain-containing protein and an essential component of the SETD1 histone H3K4 methyltransferase complex. CXXC domain proteins direct different chromatin-modifying activities to various chromatin regions. Here, we report crystal structures of the CFP1 CXXC domain in complex with six different CpG DNA sequences. The crescent-shaped CFP1 CXXC domain is wedged into the major groove of the CpG DNA, distorting the B-form DNA, and interacts extensively with the major groove of the DNA. The structures elucidate the molecular mechanism of the non-methylated CpG-binding specificity of the CFP1 CXXC domain. The CpG motif is confined by a tripeptide located in a rigid loop, which only allows the accommodation of the non-methylated CpG dinucleotide. Furthermore, we demonstrate that CFP1 has a preference for a guanosine nucleotide following the CpG motif.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Binding Sites
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Cell Nucleus / genetics
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Cell Nucleus / metabolism
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Chromatin / genetics
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Chromatin / metabolism
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Cloning, Molecular
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CpG Islands / genetics*
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Crystallization
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Crystallography, X-Ray
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DNA / chemistry
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DNA / metabolism*
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DNA Methylation
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DNA-Binding Proteins* / genetics
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DNA-Binding Proteins* / metabolism
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Escherichia coli
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Histones / genetics
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Histones / metabolism
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Humans
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Models, Molecular
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Molecular Sequence Data
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Oligopeptides / genetics
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Oligopeptides / metabolism
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Protein Binding / genetics
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Protein Structure, Tertiary
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Recombinant Proteins* / genetics
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Recombinant Proteins* / metabolism
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Sequence Alignment
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Structure-Activity Relationship
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Trans-Activators
Substances
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CXXC1 protein, human
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Chromatin
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DNA-Binding Proteins
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Histones
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Oligopeptides
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Recombinant Proteins
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Trans-Activators
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DNA