Epigenetic Modifications of Cytosine: Biophysical Properties, Regulation, and Function in Mammalian DNA

Jack S. Hardwick, Andrew N. Lane, Tom Brown

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


To decode the function and molecular recognition of several recently discovered cytosine derivatives in the human genome – 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine – a detailed understanding of their effects on the structural, chemical, and biophysical properties of DNA is essential. Here, we review recent literature in this area, with particular emphasis on features that have been proposed to enable the specific recognition of modified cytosine bases by DNA-binding proteins. These include electronic factors, modulation of base-pair stability, flexibility, and radical changes in duplex conformation. We explore these proposals and assess whether or not they are supported by current biophysical data. This analysis is focused primarily on the properties of epigenetically modified DNA itself, which provides a basis for discussion of the mechanisms of recognition by different proteins.

Original languageEnglish
Article number1700199
Issue number3
StatePublished - Mar 2018

Bibliographical note

Funding Information:
Research of the authors is supported by an Oxford University/EPSRC Doctoral Training Partnership award (to J.S.H.), a Carmen L. Buck endowment (to A.N.L.), and a BBSRC sLoLa grant BB/J001694/2 – Extending the boundaries of nucleic acid chemistry (to T.B.).

Publisher Copyright:
© 2018 WILEY Periodicals, Inc.


  • 5-carboxylcytosine
  • 5-formylcytosine
  • 5-hydroxymethylcytosine
  • 5-methylcytosine
  • DNA demethylation
  • DNA structure
  • epigenetics
  • thymine-DNA glycosylase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)


Dive into the research topics of 'Epigenetic Modifications of Cytosine: Biophysical Properties, Regulation, and Function in Mammalian DNA'. Together they form a unique fingerprint.

Cite this