Philip M.D. Severin, Xueqing Zou, Klaus Schulten, and Hermann E. Gaub.
Effects of cytosine hydroxymethylation on DNA strand separation.
Biophysical Journal, 104:208-215, 2013.
(PMC: 3540242)
SEVE2013
Cytosine hydroxymethylation is an epigenetic control factor in higher organisms. New
discoveries of the biological roles of hydroxymethylation raise questions about how
this epigenetic modification exerts its functions and how organisms discriminate cyto-
sine hydroxymethylation from methylation. Here, we report investigations that reveal
an effect of cytosine hydroxymethylation on mechanical properties of DNA under load.
The findings are based on molecular force assay (MFA) measurements and steered
molecular dynamics (SMD) simulations. MFA experiments identified significant effects
of hydroxymethylation on stretching-induced strand separation; the underlying phys-
ical mechanism has been revealed by SMD simulations. We find that hydroxymethy-
lation can either up-regulate or down-regulate DNAs strand separation propensity,
suggesting that hydroxymethylation can control gene expression by facilitating or ob-
structing the action of transcription machinery or the access to chromosomal DNA.
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