Epigenetic modification of cytosines fine tunes the stability of i-motif DNA

Wright, Elisé P., Abdelhamid, Mahmoud A. S., Ehiabor, Michelle O., Grigg, Melanie C., Irving, Kelly, Smith, Nicole M. and Waller, Zoë A. E. (2020) Epigenetic modification of cytosines fine tunes the stability of i-motif DNA. Nucleic Acids Research, 48 (1). pp. 55-62. ISSN 0305-1048

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Abstract

i-Motifs are widely used in nanotechnology, play a part in gene regulation and have been detected in human nuclei. As these structures are composed of cytosine, they are potential sites for epigenetic modification. In addition to 5-methyl- and 5-hydroxymethylcytosine modifications, recent evidence has suggested biological roles for 5-formylcytosine and 5-carboxylcytosine. Herein the human telomeric i-motif sequence was used to examine how these four epigenetic modifications alter the thermal and pH stability of i-motifs. Changes in melting temperature and transitional pH depended on both the type of modification and its position within the i-motif forming sequence. The cytosines most sensitive to modification were next to the first and third loops within the structure. Using previously described i-motif forming sequences, we screened the MCF-7 and MCF-10A methylomes to map 5-methylcytosine and found the majority of sequences were differentially methylated in MCF7 (cancerous) and MCF10A (non-cancerous) cell lines. Furthermore, i-motif forming sequences stable at neutral pH were significantly more likely to be epigenetically modified than traditional acidic i-motif forming sequences. This work has implications not only in the epigenetic regulation of DNA, but also allows discreet tunability of i-motif stability for nanotechnological applications.

Item Type: Article
Additional Information: © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Science
Depositing User: LivePure Connector
Date Deposited: 03 Dec 2019 02:12
Last Modified: 22 Sep 2021 01:48
URI: https://ueaeprints.uea.ac.uk/id/eprint/73233
DOI: 10.1093/nar/gkz1082

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