DNA sequence and methylation prescribe the inside-out conformational dynamics and bending energetics of DNA minicircles.

ABSTRACT: Eukaryotic genome and methylome encode DNA fragments' propensity to form nucleosome particles. Although the mechanical properties of DNA possibly orchestrate such encoding, the definite link between 'omics' and DNA energetics has remained elusive. Here, we bridge the divide by examining the sequence-dependent energetics of highly bent DNA. Molecular dynamics simulations of 42 intact DNA minicircles reveal that each DNA minicircle undergoes inside-out conformational transitions with the most likely configuration uniquely prescribed by the nucleotide sequence and methylation of DNA. The minicircles' local geometry consists of straight segments connected by sharp bends compressing the DNA's inward-facing major groove. Such an uneven distribution of the bending stress favors minimum free energ

SUBMITTER: Yoo J 

PROVIDER: S-EPMC8599915 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature