Los Alamos National Laboratory, Theoretical Division and Center for Nonlinear Studies, Los Alamos, NM, USA.
Nucleic Acids Res. 2010 Apr;38(6):1790-5. doi: 10.1093/nar/gkp1084. Epub 2009 Dec 17.
We assess the role of DNA breathing dynamics as a determinant of promoter strength and transcription start site (TSS) location. We compare DNA Langevin dynamic profiles of representative gene promoters, calculated with the extended non-linear PBD model of DNA with experimental data on transcription factor binding and transcriptional activity. Our results demonstrate that DNA dynamic activity at the TSS can be suppressed by mutations that do not affect basal transcription factor binding-DNA contacts. We use this effect to establish the separate contributions of transcription factor binding and DNA dynamics to transcriptional activity. Our results argue against a purely 'transcription factor-centric' view of transcription initiation, suggesting that both DNA dynamics and transcription factor binding are necessary conditions for transcription initiation.
我们评估了 DNA 呼吸动力学在决定启动子强度和转录起始位点 (TSS) 位置中的作用。我们比较了具有转录因子结合和转录活性实验数据的扩展非线性 PBD DNA 模型计算的代表性基因启动子的 DNA Langevin 动态分布,并得出结论:TSS 处的 DNA 动态活性可以被不影响基本转录因子结合-DNA 接触的突变所抑制。我们利用这种效应来确定转录因子结合和 DNA 动力学对转录活性的单独贡献。我们的结果反对纯粹的转录起始“转录因子中心”观点,表明 DNA 动力学和转录因子结合都是转录起始的必要条件。