Profiling the Thermodynamic Softness of Adenoviral Promoters

Abstract

We showed previously that anharmonic DNA dynamical features correlate with transcriptional activity in selected viral promoters, and hypothesized that areas of DNA softness may represent loci of functional significance. The nine known promoters from human adenovirus type 5 were analyzed for inherent DNA softness using the Peyrard-Bishop-Dauxois model and a statistical mechanics approach, using a transfer integral operator. We found a loosely defined pattern of softness peaks distributed both upstream and downstream of the transcriptional start sites, and that early transcriptional regions tended to be softer than late promoter regions. When reported transcription factor binding sites were superimposed on our calculated softness profiles, we observed a close correspondence in many cases, which suggests that DNA duplex breathing dynamics may play a role in protein recognition of specific nucleotide sequences and protein-DNA binding. These results suggest that genetic information is stored not only in explicit codon sequences, but also may be encoded into local dynamic and structural features, and that it may be possible to access this obscured information using DNA dynamics calculations.

Binding of Nucleoid-Associated Protein Fis to DNA Is Regulated by DNA Breathing Dynamics

“…, coherent relatively long-lived transient openings) are a characteristic feature of mammalian core promoters, see for example [37]. Sequences with a relatively high propensity to form bubbles have been found to overlap and affect transcription start sites [35], [38], [39], [40], replication origins [36], [41], correlate with TF binding sites and affect TF binding [42], [43], [44], [45], [46], [47], as well as to play role in formation of non-B-DNA structures [34] and in cytosine methylation [33] …”

Modeling the interaction of DNA with alternating fields

“…It has potential ability to describe the melting transition and denaturation bubbles of the dsDNA such as those that occur during the initial stage of the transcription process. Some specific correlation with transcription initiation sites has been claimed [22,[28][29][30][31] and debated [32,33].…”

Theoretical and Experimental Investigations of DNA Open States

“…При помощи этого метода был изучен целый ряд промоторов [268,269]. Что характерно, расчётные пики профилей нестабильности далеко не всегда совпадали с участками, ответственными за первичное взаимодействие с ферментами.…”

“…Что характерно, расчётные пики профилей нестабильности далеко не всегда совпадали с участками, ответственными за первичное взаимодействие с ферментами. В результате был сделан вывод о необходимости улучшения модели ПБД для более точного описания локальной денатурации гетерогенной ДНК [269]. Этот вывод справедлив, по крайней мере, для случая, когда профили нестабильности получают на основе расчёта равновесных термодинамических свойств модели.…”

“…Так, переход от ланжевеновской динамики к изучению равновесных свойств модели ПБД приводит к заметной потере согласия с экспериментальными данными. Это хорошо видно из результатов Van Erp et al и других исследователей [264,[267][268][269]. Им не удалось воспроизвести ни существенной гетерогенности профиля нестабильности, ни дальнего эффекта мутации, наблюдаемых в экспериментах [29,30].…”