SMAdd-seq: Probing chromatin accessibility with small molecule DNA intercalation and nanopore sequencing.

ABSTRACT: Studies of in vivo chromatin organization have relied on the accessibility of the underlying DNA to nucleases or methyltransferases, which is limited by their requirement for purified nuclei and enzymatic treatment. Here, we introduce a nanopore-based sequencing technique called Small-Molecule Adduct sequencing (SMAdd-seq), where we profile chromatin accessibility by treating nuclei or intact cells with a small molecule, angelicin. Angelicin reacts with thymine bases in linker DNA not bound to core nucleosomes after UV light exposure, thereby labeling accessible DNA regions. By applying SMAdd-seq in Saccharomyces cerevisiae, we demonstrate that angelicin-modified DNA can be detected by its distinct nanopore current signals. To systematically identify angelicin modifications a

SUBMITTER: Bai G 

PROVIDER: S-EPMC10983977 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature