Bubble lifetimes in DNA gene promoters and their mutations affecting transcription

TL;DR

This study investigates how mutations in DNA promoters influence the lifetimes of local DNA openings, revealing correlations between bubble dynamics and transcriptional activity using computational simulations.

Contribution

It introduces a detailed analysis of bubble lifetime profiles in gene promoters and mutants, linking physical DNA properties to transcription regulation.

Findings

Mutations decreasing transcription reduce bubble lifetimes at mutation sites.

Mutations increasing transcription enhance bubble lifetimes.

Bubble lifetime differences range from 20% to over 30% depending on bubble length.

Abstract

Relative lifetimes of inherent double stranded DNA openings with lengths up to ten base pairs are presented for different gene promoters and corresponding mutants that either increase or decrease transcriptional activity, in the framework of the Peyrard-Bishop-Dauxois model. Extensive microcanonical simulations are used, with energies corresponding to physiological temperature. The bubble lifetime profiles along the DNA sequences demonstrate a significant reduction of the average lifetime at the mutation sites when the mutated promoter decreases transcription, while a corresponding enhancement of the bubble lifetime is observed in the case of mutations leading to increased transcription. The relative difference of bubble lifetimes between the mutated and the wild type promoters at the position of mutation varies from 20% to more than 30% as the bubble length is decreasing