5-Formylcytosine organizes nucleosomes and forms Schiff base interactions with histones in mouse embryonic stem cells.
Springer Science and Business Media LLC
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Raiber, E., Portella Carbo, G., Martínez Cuesta, S., Hardisty, R., Murat, P., Li, Z., Iurlaro, M., et al. (2018). 5-Formylcytosine organizes nucleosomes and forms Schiff base interactions with histones in mouse embryonic stem cells.. Nat Chem, 10 (12), 1258-1266. https://doi.org/10.1038/s41557-018-0149-x
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.
Nucleosomes, Animals, Mice, Schiff Bases, Cytosine, Histones, DNA, Mouse Embryonic Stem Cells
Wellcome Trust (099232/Z/12/Z)
Medical Research Council (MC_PC_12009)
External DOI: https://doi.org/10.1038/s41557-018-0149-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286194