title: DNA G-quadruplexes show strong interaction with DNA methyltransferases in vitro.
abstract: The DNA methyltransferase enzymes (DNMTs) catalyzing cytosine methylation do so at specific locations of the genome, although with some level of redundancy. The de novo methyltransferases DNMT3A and 3B play a vital role in methylating the genome of the developing embryo in regions devoid of methylation marks. The ability of DNMTs to colocalize at sites of DNA damage is suggestive that recognition of mispaired bases and unusual structures is inherent to the function of these proteins. We provide evidence for G-quadruplex formation within imprinted gene promoters, and report high-affinity binding of recombinant human DNMTs to such DNA G-quadruplexes in vitro. These observations suggest a potential interaction of G-quadruplexes with the DNA methylation machinery, which may be of epigenetic and biological significance.
authors.affiliation: Department of Pathology, University of Otago, Christchurch, New Zealand.
authors.forename: Simone L
authors.initials: SL
authors.lastname: Cree
authors.affiliation: Department of Chemical and Process Engineering, University of Canterbury, Christchurch, New Zealand.|Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand.
authors.forename: Rayleen
authors.initials: R
authors.lastname: Fredericks
authors.affiliation: Department of Pathology, University of Otago, Christchurch, New Zealand.
authors.forename: Allison
authors.initials: A
authors.lastname: Miller
authors.affiliation: Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand.|School of Biological Sciences, University of Canterbury, Christchurch, New Zealand.
authors.forename: F Grant
authors.initials: FG
authors.lastname: Pearce
authors.affiliation: Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Filichev
authors.affiliation: Department of Chemical and Process Engineering, University of Canterbury, Christchurch, New Zealand.|Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand.
authors.forename: Conan
authors.initials: C
authors.lastname: Fee
authors.affiliation: Department of Pathology, University of Otago, Christchurch, New Zealand.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Kennedy
mesh_terms: D003596:Cytosine / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D054856:G-Quadruplexes; D015894:Genome, Human; D006801:Humans; D000097584:DNA Methyltransferase 3B
chemical_list: D003596:Cytosine; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human
keywords: DNA methylation; G-quadruplex; genomic imprinting; protein-DNA interaction