Understanding the structural and dynamic consequences of DNA epigenetic modifications : Computational insights into cytosine methylation and hydroxymethylation

• 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.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

DNA methylation

epigenetics

indirect readout

molecular dynamics

recognition

AFM

Atomic Force Microscopy

DDD

Dickerson-Drew Dodecamer

DFT

Density Functional Theory

DNA

Deoxyribonucleic Acid

DNMT

DNA Methyltransferase

LINEs

Long Interspred Transposable Elements

MD

MeCP

Methylated CpG-binding proteins

MM

Molecular Mechanics

PBC

Periodic Boundary Conditions

QM

Quantum Mechanics

RDF

Radial Distribution Functions

RESP

Restrained Electrostatic Potentials Model

SINEs

Short Interspred Transposable Elements

SPME

Smooth Particle-Mesh Ewald

TET

Translocation Proteins

WT

Wild Type

Publikations- och innehållstyp

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