Yella Venkata Rajesh, Bansal Manju
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, India.
J Bioinform Comput Biol. 2013 Dec;11(6):1343001. doi: 10.1142/S0219720013430014. Epub 2013 Dec 2.
Gene expression is the most fundamental biological process, which is essential for phenotypic variation. It is regulated by various external (environment and evolution) and internal (genetic) factors. The level of gene expression depends on promoter architecture, along with other external factors. Presence of sequence motifs, such as transcription factor binding sites (TFBSs) and TATA-box, or DNA methylation in vertebrates has been implicated in the regulation of expression of some genes in eukaryotes, but a large number of genes lack these sequences. On the other hand, several experimental and computational studies have shown that promoter sequences possess some special structural properties, such as low stability, less bendability, low nucleosome occupancy, and more curvature, which are prevalent across all organisms. These structural features may play role in transcription initiation and regulation of gene expression. We have studied the relationship between the structural features of promoter DNA, promoter directionality and gene expression variability in S. cerevisiae. This relationship has been analyzed for seven different measures of gene expression variability, along with two different regulatory effect measures. We find that a few of the variability measures of gene expression are linked to DNA structural properties, nucleosome occupancy, TATA-box presence, and bidirectionality of promoter regions. Interestingly, gene responsiveness is most intimately correlated with DNA structural features and promoter architecture.
基因表达是最基本的生物学过程,对表型变异至关重要。它受各种外部(环境和进化)和内部(遗传)因素调控。基因表达水平取决于启动子结构以及其他外部因素。序列基序的存在,如转录因子结合位点(TFBSs)和TATA框,或脊椎动物中的DNA甲基化,已被认为与真核生物中某些基因的表达调控有关,但大量基因缺乏这些序列。另一方面,一些实验和计算研究表明,启动子序列具有一些特殊的结构特性,如低稳定性、低柔韧性、低核小体占有率和更大的曲率,这些特性在所有生物体中都很普遍。这些结构特征可能在转录起始和基因表达调控中发挥作用。我们研究了酿酒酵母中启动子DNA的结构特征、启动子方向性与基因表达变异性之间的关系。针对七种不同的基因表达变异性测量方法以及两种不同的调控效应测量方法,分析了这种关系。我们发现,一些基因表达变异性测量方法与DNA结构特性、核小体占有率、TATA框的存在以及启动子区域的双向性有关。有趣的是,基因反应性与DNA结构特征和启动子结构最为密切相关。