Light-based footprinting of a eukaryotic genome.

Authors

Linnea Ögren, Isabella Muylaert, Kerryn Elliott, Erik Larsson

Published in

Science advances. Volume 12. Issue 26. Pages eaec0059. Jun 26, 2026. Epub Jun 24, 2026.

Abstract

Identification of protein-bound DNA sites is key to understanding genome function and regulation, but studying protein-DNA interactions in living, unperturbed cells remains challenging. UV footprinting has been used to study such interactions in vivo by detecting changes in DNA photoproduct formation at protein-bound sites, but only on a limited scale. Here, we describe whole-genome deamination sequencing (Deam-seq), wherein photoproducts (pyrimidine dimers) induced by UV irradiation are revealed as mutations, enabling generation of quantitative photofootprints of the yeast Saccharomyces cerevisiae at ultradeep coverage. By comparing cellular and naked DNA, we find that this approach can resolve protein occupancy at high resolution without preference toward accessible regions. Cell/naked differential signals commonly aligned with predicted regulatory sites, ChIP peaks and DNase I protection footprints, and supported that yeast DNA binding proteins typically exhibit protective effects on UV damage. Our results provide proof of concept for using light and sequencing to study protein-DNA interactions in their native cellular context at genome scale.

PMID:
42341124
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

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