High-precision mapping reveals rare N⁶-deoxyadenosine methylation in the mammalian genome.

ABSTRACT: N⁶-deoxyadenosine methylation (6mA) is the most widespread type of DNA modification in prokaryotes and is also abundantly distributed in some unicellular eukaryotes. However, 6mA levels are remarkably low in mammals. The lack of a precise and comprehensive mapping method has hindered more advanced investigations of 6mA. Here, we report a new method MM-seq (modification-induced mismatch sequencing) for genome-wide 6mA mapping based on a novel detection principle. We found that modified DNA bases are prone to form a local open region that allows capture by antibody, for example, via a DNA breathing or base-flipping mechanism. Specified endonuclease or exonuclease can recognize the antibody-stabilized mismatch-like structure and mark the exact modified sites for sequencing readout.

SUBMITTER: Chen LQ 

PROVIDER: S-EPMC9794812 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature