5-Formylcytosine organizes nucleosomes and forms Schiff base interactions with histones in mouse embryonic stem cells

Raiber, E.-A. et al. (2018) 5-Formylcytosine organizes nucleosomes and forms Schiff base interactions with histones in mouse embryonic stem cells. Nature Chemistry, 10, pp. 1258-1266. (doi: 10.1038/s41557-018-0149-x) (PMID:30349137)

Abstract

Nucleosomes are the basic unit of chromatin that help the packaging of genetic material while controlling access to the genetic information. The underlying DNA sequence, together with transcription-associated proteins and chromatin remodelling complexes, are important factors that influence the organization of nucleosomes. Here, we show that the naturally occurring DNA modification, 5-formylcytosine (5fC) is linked to tissue-specific nucleosome organization. Our study reveals that 5fC is associated with increased nucleosome occupancy in vitro and in vivo. We demonstrate that 5fC-associated nucleosomes at enhancers in the mammalian hindbrain and heart are linked to elevated gene expression. Our study also reveals the formation of a reversible-covalent Schiff base linkage between lysines of histone proteins and 5fC within nucleosomes in a cellular environment. We define their specific genomic loci in mouse embryonic stem cells and look into the biological consequences of these DNA-histone Schiff base sites. Collectively, our findings show that 5fC is a determinant of nucleosome organization and plays a role in establishing distinct regulatory regions that control transcription.

• Item Type: Articles
• Additional Information: S.B. is a senior investigator of the Wellcome Trust (grant no. 099232/z/12/z). The Balasubramanian laboratory is also supported by core funding from Cancer Research UK (C14303/A17197). Z.L. is supported by a studentship from A*STAR (Singapore). M.A.D is supported by the Leukaemia Foundation Australia senior fellowship and Howard Hughes Medical Institute international research scholarship. The Reik laboratory is supported by BBSRC (BB/ K010867/1) and the Wellcome Trust (095645/Z/11/Z).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Beraldi, Dr Dario
• Authors: Raiber, E.-A., Portella, G., Martínez Cuesta, S., Hardisty, R., Murat, P., Li, Z., Iurlaro, M., Dean, W., Spindel, J., Beraldi, D., Liu, Z., Dawson, M. A., Reik, W., and Balasubramanian, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Chemistry
• Publisher: Nature Research
• ISSN: 1755-4330
• ISSN (Online): 1755-4349
• Published Online: 22 October 2018
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Nature Chemistry 10:1258-1266
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher