Sequence-dependent geometric flexibility of core promoter regions in human genome

来源 :第五届全国生物信息学与系统生物学学术大会 | 被引量 : 0次 | 上传用户:qb54223322
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  Background: The general framework of promoter mechanism is dependent on protein-DNA interaction in which the different transcription factors (TFs) bind on the promoter region to enable its activity.Although many studies have been taken on this area, the mechanism of transcription regular is still obscure.Hence it is necessary to investigate promoter sequences in higher dimensions than the sequence alone.Dataset and Methods: The 4263 CpG related and 1683 non-CpG related human promoters were downloaded from the UCSC Genome Browser(http://genome.ucsc.edu/).The sequences with 4001bp length from 2000bp upstream to 2000bp downstream of the transcription start sites (TSSs the 0th sites) were selected as the core promoters.Based on the physical potentials derived from quantum chemical calculations of atomic molecular dynamics (MD) simulations, In this study we introduced physical structural variables by defining three displacements (rise, shift and slide) and three rotation angles (twist, roll and tilt) for each dinucleotide to describe transcription initiation of human promoter.Results: Using 16 experimental parameters of nearest-neighbor dinucleotides based on the structural models, we converted the core-promoter sequence into a string of numerical values for studying the structural flexibility.The analysis results reveal that there are significant difference of structural patterns between the CpG related and non-CpG related promoter region, which indicated that the thermodynamic mechanism of transcription initiation for CpG related and non-CpG gene may be distinctively.We clearly observed that the structure profiles of CpG related promoter have the enhanced stiffness or flexibility than the non-CpG related promoter, particular in the shift profile and the twist profile.We believe that the six flexibility parameters will be helpful for further elucidating the transcription initiation regulation and improving the identification accuracy of human promoter .
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