Effects of cytosine hydroxymethylation on DNA strand separation.

Cytosine hydroxymethylation is an epigenetic control factor in higher organisms. New discoveries of the biological roles of hydroxymethylation serve to raise questions about how this epigenetic modification exerts its functions and how organisms discriminate cytosine 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 measurements and steered molecular dynamics simulations. Molecular force assay experiments identified significant effects of hydroxymethylation on stretching-induced strand separation; the underlying physical mechanism has been revealed by steered molecular dynamics simulations. We find that hydroxymethylation can either upregulate or downregulate DNA's strand separation propensity, suggesting that hydroxymethylation can control gene expression by facilitating or obstructing the action of transcription machinery or the access to chromosomal DNA.