Nussinov R
Laboratory of Mathematical Biology, Frederick Cancer, Research and Development Center, Maryland 21702-1201.
J Theor Biol. 1992 Mar 21;155(2):243-70. doi: 10.1016/s0022-5193(05)80597-1.
Regulation of RNA transcription in eukaryotic polymerase II promoters involves a complex assembly of protein factors. Some of the factors bind to their cognate DNA-sequence elements while others mediate between the DNA bound ones. In order to enable protein-protein interaction, their spatial positioning with respect to each other is critical. Here two DNA-sequence-elements are investigated, the CCAAT and the TATA boxes and their spacers. Whereas the position of the TATA is fixed at about -30, that of the CCAAT can vary substantially from -50 to -200. Despite the variable loop sizes, the CTF (CCAAT-binding) protein interacts--either directly or indirectly via a co-activator--with the general basal TATA-binding transcription factors. Sequence analysis of the spacers, as a function of their sizes, reveals that in the upstream regions of the spacers RR and YY are abundant. In the downstream, 3' region of the spacers RY and YR are very frequent. The DNA sequence elements and their intervening spacers are analyzed in terms of their geometry, anisotropic flexibility and local superhelical density. Our results indicate that the CCAAT and its vicinity is rigid, whereas the TATA and its surroundings is flexible. It is the large flexibility of this region in twist and in roll which allows DNA looping. General mechanistic implications for pol II promoters are discussed.
真核生物聚合酶II启动子中RNA转录的调控涉及蛋白质因子的复杂组装。一些因子与其同源DNA序列元件结合，而其他因子则在与DNA结合的因子之间起介导作用。为了实现蛋白质-蛋白质相互作用，它们彼此之间的空间定位至关重要。这里研究了两个DNA序列元件，即CCAAT盒和TATA盒及其间隔区。TATA的位置固定在约-30处，而CCAAT的位置在-50至-200之间可大幅变化。尽管环的大小可变，但CTF（CCAAT结合）蛋白直接或通过共激活因子间接与一般基础TATA结合转录因子相互作用。对间隔区进行序列分析，作为其大小的函数，发现在间隔区的上游区域RR和YY丰富。在间隔区的下游3'区域，RY和YR非常常见。根据其几何形状、各向异性柔韧性和局部超螺旋密度对DNA序列元件及其间隔区进行了分析。我们的结果表明，CCAAT及其附近区域是刚性的，而TATA及其周围区域是柔性的。正是该区域在扭曲和滚动方面的大柔韧性允许DNA环化。讨论了对聚合酶II启动子的一般机制影响。
