PT  - JOURNAL ARTICLE
AU  - Eun-Ang Raiber
AU  - Guillem Portella
AU  - Sergio Martínez Cuesta
AU  - Robyn Hardisty
AU  - Pierre Murat
AU  - Zhe Li
AU  - Mario Iurlaro
AU  - Wendy Dean
AU  - Julia Spindel
AU  - Dario Beraldi
AU  - Mark A. Dawson
AU  - Wolf Reik
AU  - Shankar Balasubramanian
TI  - 5-Formylcytosine controls nucleosome positioning through covalent histone-DNA interaction
AID  - 10.1101/224444
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 224444
4099  - http://biorxiv.org/content/early/2017/11/24/224444.short
4100  - http://biorxiv.org/content/early/2017/11/24/224444.full
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.