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

Elise P. Wright, Mahmoud A. S. Abdelhamid, Michelle O. Ehiabor, Melanie Grigg, Kelly Irving, Nicole Smith, Zoe A. E. Waller

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.
Original languageEnglish
Number of pages8
JournalNucleic Acids Research
Volume48
Issue number1
Publication statusPublished - 10 Jan 2020

Fingerprint

Nucleotide Motifs
Cytosine
Epigenomics
5-Methylcytosine
Nanotechnology
Freezing
Hot Temperature
Cell Line
Temperature
DNA
Genes

Cite this

Wright, E. P., Abdelhamid, M. A. S., Ehiabor, M. O., Grigg, M., Irving, K., Smith, N., & Waller, Z. A. E. (2020). Epigenetic modification of cytosines fine tunes the stability of i-motif DNA. Nucleic Acids Research, 48(1).
Wright, Elise P. ; Abdelhamid, Mahmoud A. S. ; Ehiabor, Michelle O. ; Grigg, Melanie ; Irving, Kelly ; Smith, Nicole ; Waller, Zoe A. E. / Epigenetic modification of cytosines fine tunes the stability of i-motif DNA. In: Nucleic Acids Research. 2020 ; Vol. 48, No. 1.
@article{1670f5d16df8454bbf02cf28ce53f5a7,
title = "Epigenetic modification of cytosines fine tunes the stability of i-motif DNA",
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.",
author = "Wright, {Elise P.} and Abdelhamid, {Mahmoud A. S.} and Ehiabor, {Michelle O.} and Melanie Grigg and Kelly Irving and Nicole Smith and Waller, {Zoe A. E.}",
year = "2020",
month = "1",
day = "10",
language = "English",
volume = "48",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "OXFORD UNIV PRESS UNITED KINGDOM",
number = "1",

}

Wright, EP, Abdelhamid, MAS, Ehiabor, MO, Grigg, M, Irving, K, Smith, N & Waller, ZAE 2020, 'Epigenetic modification of cytosines fine tunes the stability of i-motif DNA' Nucleic Acids Research, vol. 48, no. 1.

Epigenetic modification of cytosines fine tunes the stability of i-motif DNA. / Wright, Elise P.; Abdelhamid, Mahmoud A. S.; Ehiabor, Michelle O.; Grigg, Melanie; Irving, Kelly; Smith, Nicole; Waller, Zoe A. E.

In: Nucleic Acids Research, Vol. 48, No. 1, 10.01.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Epigenetic modification of cytosines fine tunes the stability of i-motif DNA

AU - Wright, Elise P.

AU - Abdelhamid, Mahmoud A. S.

AU - Ehiabor, Michelle O.

AU - Grigg, Melanie

AU - Irving, Kelly

AU - Smith, Nicole

AU - Waller, Zoe A. E.

PY - 2020/1/10

Y1 - 2020/1/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85077484996&partnerID=8YFLogxK

M3 - Article

VL - 48

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 1

ER -

Wright EP, Abdelhamid MAS, Ehiabor MO, Grigg M, Irving K, Smith N et al. Epigenetic modification of cytosines fine tunes the stability of i-motif DNA. Nucleic Acids Research. 2020 Jan 10;48(1).