Milani Pascale, Marilley Monique, Rocca-Serra José
RGFCP EA 3290, Faculté de Médecine, Université de la Méditerranée, 27, Bvd Jean Moulin, 13385 Marseille cedex 5, France.
Biochimie. 2007 Apr;89(4):528-33. doi: 10.1016/j.biochi.2006.12.004. Epub 2006 Dec 31.
DNA is not only a nucleotide sequence which allows the binding of regulators but its intrinsic structural properties such as curvature and flexibility are also viewed as playing an active role in the regulation of transcription. Our combination of computer modelling and AFM imaging allow direct access to DNA curvature and flexibility. We have searched for these DNA structural features involved in transcription regulation within the IL-2Ralpha gene promoter. Investigation of these structural characteristics shows concordant results. First, in the core promoter, the region containing the functional TATA box shows intrinsic curvature associated with a peculiar distribution of flexibility. Both these inherent properties are characteristic of this region as compared with the other parts of the promoter. Second, the proximal promoter exhibits two important regions: a first one flexible and curved, followed by a segment of rigid linear DNA, each localised within one of the two Positive Regulatory Regions PRRI and PRRII respectively. Based on these observations, we propose different roles for DNA curvature and/or flexibility in promoter sequences.
DNA不仅是一种能让调节因子结合的核苷酸序列,其内在的结构特性,如弯曲度和柔韧性,也被认为在转录调控中发挥着积极作用。我们将计算机建模与原子力显微镜成像相结合,得以直接了解DNA的弯曲度和柔韧性。我们在白细胞介素-2受体α基因启动子内寻找这些参与转录调控的DNA结构特征。对这些结构特征的研究显示出一致的结果。首先,在核心启动子中,包含功能性TATA框的区域呈现出与特殊柔韧性分布相关的内在弯曲度。与启动子的其他部分相比,这两种固有特性都是该区域的特征。其次,近端启动子呈现出两个重要区域:第一个区域柔韧且弯曲,随后是一段刚性线性DNA,它们分别位于两个正向调节区域PRRI和PRRII之一内。基于这些观察结果,我们提出了DNA弯曲度和/或柔韧性在启动子序列中的不同作用。