engleski

Structure-function relationship between flexibility and transcription initiation and termination in human and fruit fly DNA

DNA flexibility is known to have a role in some biologically important molecular processes like chromosome packaging and trancription. DNA curvature and bendability are sequence-dependent intrinsic flexibility properties of a DNA molecule. DNA curvature is shortly described as torsional flexibility and bendability as an anisotropic bending flexibility of a helix. Several published studies linked curvature and bendability with transcription initiation and termination in bacterial and less in eukaryotic genes. The main goal of our research was to computationally observe if there is a specific structural signal in proximity to transcription initiation and termination sites of fruit fly and human DNA sequences. Our hypothesis was that a localized change in curvature and flexibility should be visible on the whole genomic level. We used fruit fly and human genomic sequences of known genes to calculate their respective curvature and bendability profiles and assess the influence that flexibility might have on transcription initiation and termination. Curvature and bendability profiles were calculated for all sequences using Atlas, a program developed inside our group, with an implemented BEND algorithm(1). Human and fruit fly promoters were also grouped by certain characteristics and analyzed separately to observe if there are differences in curvature and bendability dependent on a promoter type. The results of our study were consistent with our hypothesis, showing a significant intrinsic signal in both curvature and bendability for transcription initiation sites, as well as transcription termination sites in human and fruit fly profiles. Also, in fruit fly, certain curvature and bendability profiles showed distinct difference in signal strength and localization with regard to a promoter type. Overall, our results show there is a clear localized structural change in proximity to transcription initiation and termination sites on a genomic level and suggest that DNA flexibilty has a role in eukaryotic transcription regulation.

DNA; curvature; bendability; transcription

nije evidentirano