Predictions of DNA mechanical properties at a genomic scale reveal potentially new functional roles of DNA-flexibility

Abstract

Mechanical properties of DNA have been implied to influence many its biological functions. Recently, a new high-throughput method, called loop-seq, that allows measuring the intrinsic bendability of DNA fragments, has been developed. Using loop-seq data, we created a deep learning model to explore the biological significance of local DNA flexibility in a range of different species from different kingdoms. Consistently, we observed a characteristic and largely nucleotide-composition-driven change of local flexibility near transcription start sites. No evidence of a generally present region of lowered flexibility upstream of transcription start sites to facilitate transcription factor binding was found. Yet, depending on the actual transcription factor investigated, flanking-sequence-dependent DNA flexibility was identified as a potential factor influencing binding. Compared to randomized genomic sequences, depending on species and taxa, actual genomic sequences were observed both with increased and lowered flexibility. Furthermore, in Arabidopsis thaliana, crossing-over and mutation rates, both de novo and fixed, were found to be linked to rigid sequence regions. Our study presents a range of significant correlations between characteristic DNA mechanical properties and genomic features, the significance of which with regard to detailed molecular relevance awaits further experimental and theoretical exploration.