Understanding the structural and dynamic consequences of DNA epigenetic modifications : Computational insights into cytosine methylation and hydroxymethylation
Carvalho, Alexandra T P ; Gouveia, Leonor ; Kanna, Charan Raju ; Wärmländer, Sebastian K T S ; Platts, Jamie A and Kamerlin, Shina Caroline Lynn LU
(2014)
In Epigenetics
9(12).
p.12-1604
- Abstract
We report a series of molecular dynamics (MD) simulations of up to a microsecond combined simulation time designed to probe epigenetically modified DNA sequences. More specifically, by monitoring the effects of methylation and hydroxymethylation of cytosine in different DNA sequences, we show, for the first time, that DNA epigenetic modifications change the molecule's dynamical landscape, increasing the propensity of DNA toward different values of twist and/or roll/tilt angles (in relation to the unmodified DNA) at the modification sites. Moreover, both the extent and position of different modifications have significant effects on the amount of structural variation observed. We propose that these conformational differences, which are... (More)
We report a series of molecular dynamics (MD) simulations of up to a microsecond combined simulation time designed to probe epigenetically modified DNA sequences. More specifically, by monitoring the effects of methylation and hydroxymethylation of cytosine in different DNA sequences, we show, for the first time, that DNA epigenetic modifications change the molecule's dynamical landscape, increasing the propensity of DNA toward different values of twist and/or roll/tilt angles (in relation to the unmodified DNA) at the modification sites. Moreover, both the extent and position of different modifications have significant effects on the amount of structural variation observed. We propose that these conformational differences, which are dependent on the sequence environment, can provide specificity for protein binding.
(Less)
- author
- Carvalho, Alexandra T P
; Gouveia, Leonor
; Kanna, Charan Raju
; Wärmländer, Sebastian K T S
; Platts, Jamie A
and Kamerlin, Shina Caroline Lynn
LU
- publishing date
- 2014-12
- type
- Contribution to journal
- publication status
- published
- keywords
- 5-Methylcytosine/chemistry, CpG Islands, Cytosine/analogs & derivatives, DNA/chemistry, DNA Methylation, Epigenesis, Genetic, Models, Molecular, Molecular Dynamics Simulation, Nucleic Acid Conformation, Protein Binding
- in
- Epigenetics
- volume
- 9
- issue
- 12
- pages
- 9 pages
- publisher
- Taylor & Francis
- external identifiers
-
- scopus:84922041576
- pmid:25625845
- ISSN
- 1559-2294
- DOI
- 10.4161/15592294.2014.988043
- language
- English
- LU publication?
- no
- id
- 10955526-b5d6-42fe-9bed-0ea569feef1b
- date added to LUP
- 2025-01-11 21:45:18
- date last changed
- 2025-06-29 18:17:46
@article{10955526-b5d6-42fe-9bed-0ea569feef1b,
abstract = {{<p>We report a series of molecular dynamics (MD) simulations of up to a microsecond combined simulation time designed to probe epigenetically modified DNA sequences. More specifically, by monitoring the effects of methylation and hydroxymethylation of cytosine in different DNA sequences, we show, for the first time, that DNA epigenetic modifications change the molecule's dynamical landscape, increasing the propensity of DNA toward different values of twist and/or roll/tilt angles (in relation to the unmodified DNA) at the modification sites. Moreover, both the extent and position of different modifications have significant effects on the amount of structural variation observed. We propose that these conformational differences, which are dependent on the sequence environment, can provide specificity for protein binding.</p>}},
author = {{Carvalho, Alexandra T P and Gouveia, Leonor and Kanna, Charan Raju and Wärmländer, Sebastian K T S and Platts, Jamie A and Kamerlin, Shina Caroline Lynn}},
issn = {{1559-2294}},
keywords = {{5-Methylcytosine/chemistry; CpG Islands; Cytosine/analogs & derivatives; DNA/chemistry; DNA Methylation; Epigenesis, Genetic; Models, Molecular; Molecular Dynamics Simulation; Nucleic Acid Conformation; Protein Binding}},
language = {{eng}},
number = {{12}},
pages = {{12--1604}},
publisher = {{Taylor & Francis}},
series = {{Epigenetics}},
title = {{Understanding the structural and dynamic consequences of DNA epigenetic modifications : Computational insights into cytosine methylation and hydroxymethylation}},
url = {{http://dx.doi.org/10.4161/15592294.2014.988043}},
doi = {{10.4161/15592294.2014.988043}},
volume = {{9}},
year = {{2014}},
}