Work

5-Formylcytosine functions as a chemical regulator of nucleosome positioning

Year: 2026

Type: article

Abstract: 5-Formylcytosine (5fC) has attracted increasing attention because of discoveries of its unique epigenetic functions as a gene activation marker beyond its role as an intermediate in the demethylation of 5-methylcytosine (5mC). However, there are scant clues to understanding the mechanisms by which 5fC affects nucleosome structures for regulating gene expression, except that 5fC promotes nucleosome formation and cross-linking with histone units via a Schiff base. The present study demonstrates that 5fC acts as a chemical cue that modulates the nucleosome positions preferred by a given DNA sequence. A series of nucleosomes designed with linker regions and 5fC at defined sites allowed systematic evaluation of the effect of formylation on the nucleosome positions, revealing site-dependent impacts of 5fC distinct from those of 5mC. The 5fC-mediated changes of relative preference for the possible nucleosome positions were not only associated with the cross-linking with histone units, but also energetic tolerance that was imparted by 5fC in terms of the base-stacking interaction against the DNA configuration characteristic at specific sites of nucleosomal DNA. These findings provide chemical insights into the regulatory mechanisms underlying 5fC-mediated nucleosome repositioning and gene expression in important biological events, such as cellular reprogramming.

Source: Nature Communications

DOI: 10.1038/s41467-026-73755-0

Authors: Takafumi Furuhata, Yijing Lin, Genki Hino, Akimitsu Okamoto

Institution: The University of Tokyo

Language: English

Topic: Epigenetics and DNA Methylation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $6,990

Funders: Japan Society for the Promotion of Science, Japan Science and Technology Agency, ACT-X