Nucleosome wrapping energy in CpG islands and the role of epigenetic base modifications.

Abstract

The majority of vertebrate promoters have a distinct DNA composition, known as a CpG island. Cytosine methylation in promoter CpG islands is associated with a substantial reduction of transcription initiation. We hypothesise that both atypical sequence composition and epigenetic base modifications may affect the mechanical properties of DNA in CpG islands, influencing the ability of proteins to bind and initiate transcription. In this work, we model two scalar measures of the sequence-dependent propensity of DNA to wrap into nucleosomes: the energy of DNA required to assume a particular nucleosomal configuration and a measure related to the probability of linear DNA spontaneously reaching the nucleosomal configuration. We find that CpG density and modification state can alter DNA mechanics by creating states more or less compatible with nucleosome formation.