RT Journal Article
SR Electronic
T1 5-Formylcytosine controls nucleosome positioning through covalent histone-DNA interaction
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 224444
DO 10.1101/224444
A1 Eun-Ang Raiber
A1 Guillem Portella
A1 Sergio Martínez Cuesta
A1 Robyn Hardisty
A1 Pierre Murat
A1 Zhe Li
A1 Mario Iurlaro
A1 Wendy Dean
A1 Julia Spindel
A1 Dario Beraldi
A1 Mark A. Dawson
A1 Wolf Reik
A1 Shankar Balasubramanian
YR 2017
UL http://biorxiv.org/content/early/2017/11/24/224444.abstract
AB Nucleosomes are the basic unit of chromatin that ensure genome integrity and control access to the genetic information. The organization of nucleosomes is influenced by the underlying DNA sequence itself, transcription factors or other transcriptional machinery associated proteins and chromatin remodeling complexes (1–4). Herein, we show that the naturally occurring DNA modification, 5-formylcytosine (5fC) contributes to the positioning of nucleosomes. We show that the ability of 5fC to position nucleosomes in vitro is associated with the formation of covalent interactions between histone residues and 5fC in the form of Schiff bases. We demonstrate that similar interactions can occur in a cellular environment and define their specific genomic loci in mouse embryonic stem cells. Collectively, our findings identify 5fC as a determinant of nucleosomal organization in which 5fC plays a role in establishing distinct regulatory regions that are linked to gene expression Our study provides a previously unknown molecular mechanism, involving the formation of reversible-covalent bonds between chromatin and DNA that supports a molecular linkage between DNA sequence, DNA base modification and chromatin structure.