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Issue 20, 2015
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Regulation of telomeric i-motif stability by 5-methylcytosine and 5-hydroxymethylcytosine modification

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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.

Graphical abstract: Regulation of telomeric i-motif stability by 5-methylcytosine and 5-hydroxymethylcytosine modification

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Supplementary files

Article information


Submitted
22 Dec 2014
Accepted
30 Mar 2015
First published
31 Mar 2015

Org. Biomol. Chem., 2015,13, 5646-5651
Article type
Paper
Author version available

Regulation of telomeric i-motif stability by 5-methylcytosine and 5-hydroxymethylcytosine modification

B. Xu, G. Devi and F. Shao, Org. Biomol. Chem., 2015, 13, 5646
DOI: 10.1039/C4OB02646B

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