title: The structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain.
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.
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.forename: Chuanbing
authors.initials: C
authors.lastname: Bian
authors.forename: Robert
authors.initials: R
authors.lastname: Lam
authors.forename: Aiping
authors.initials: A
authors.lastname: Dong
authors.forename: Jinrong
authors.initials: J
authors.lastname: Min
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D018899:CpG Islands / Q000235:genetics*; D003460:Crystallization; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D015534:Trans-Activators
chemical_list: C409062:CXXC1 protein, human; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D009842:Oligopeptides; D011994:Recombinant Proteins; D015534:Trans-Activators; D004247:DNA