The structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain

Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.
Nature Communications (Impact Factor: 11.47). 03/2011; 2(1):227. DOI: 10.1038/ncomms1237
Source: PubMed


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.

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Available from: Chao Xu, Sep 23, 2015
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