title: Regulation of telomeric i-motif stability by 5-methylcytosine and 5-hydroxymethylcytosine modification.
abstract: The two important epigenetic markers in the human genome, 5-methylcytosine (mC) and 5-hydroxymethylcytosine (hmC), are involved in gene regulation processes. As a major epigenetic target, cytosines in a C-rich DNA sequence were substituted with mC and hmC to investigate the thermal stability and pH sensitivity of the corresponding i-motifs. Circular Dichroism (CD) studies indicate the formation of i-motifs at acidic pH (<6.5) for mC- and hmC-modified DNA sequences. Thermal denaturation results suggest that DNA i-motifs are stabilized when modified with one or two mCs. However, hypermethylation with mC and single modification with hmC cause destabilization of the structure. A biomimetic crowding agent does not alter the stability effect trends resulting from mC and hmC modifications, though the corresponding i-motifs show elevated melting temperatures without significant changes in pKa values.
authors.affiliation: Division of Chemistry and Biological Chemistry, Nanyang Technological University, 21 Nanyang Link, Singapore 637371. fwshao@ntu.edu.sg.
authors.forename: Baochang
authors.initials: B
authors.lastname: Xu
authors.forename: Gitali
authors.initials: G
authors.lastname: Devi
authors.forename: Fangwei
authors.initials: F
authors.lastname: Shao
mesh_terms: D044503:5-Methylcytosine / Q000737:chemistry* / Q000031:analogs & derivatives; D002942:Circular Dichroism; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D019175:DNA Methylation; D006801:Humans; D059372:Nucleotide Motifs / Q000235:genetics*; D017434:Protein Structure, Tertiary; D016615:Telomere / Q000737:chemistry / Q000235:genetics*; D013696:Temperature
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA