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 of its biological functions. Recently, a new high-throughput method, called loop-seq, which 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 dinucleotide-composition-driven change of local flexibility near transcription start sites. In the presence of a TATA-box, a pronounced peak of high flexibility can be observed. Furthermore, depending on the transcription factor investigated, flanking-sequence-dependent DNA flexibility was identified as a potential factor influencing DNA 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, mutation rates, both de novo and fixed, were found to be associated with relatively 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 theoretical and experimental exploration.