Topological epigenetics: The biophysics of DNA supercoiling and its relation to transcription and genome instability

Abstract

Whilst DNA encodes our genetic blueprint as individual nucleobases, as well as epigenetic annotations in the form of biochemical marks, it also carries an extra layer of topological information –, the local over or underwinding of the double helix, known as DNA supercoiling. Supercoiling is a fundamental property of DNA that can be viewed as “topological epigenetics”: it stores energy and structural information, and is tightly linked to fundamental processes; however, its quantification and study, by experiments and modelling alike, is challenging. We review experimental and simulation techniques to study supercoiling and its partition into twist and writhe, especially in the context of chromatin. We then discuss the dynamics of transcription-driven supercoiling in vitro and in vivo, and of supercoiling propagation along mammalian genomes. We finally provide evidence from the literature and potential mechanisms linking this ethereal topological mark to gene expression and chromosome instabilities in genetic diseases and cancer.