Transcriptional and structural impact of TATA-initiation site spacing in mammalian core promoters.
Transcriptional and structural impact of TATA-initiation site spacing in mammalian core promoters.
复制标题
DOI：
10.1186/gb-2006-7-8-r78
复制
发表时间：
2006
期刊：
影响因子：
12.3
通讯作者：
Sandelin, Albin
中科院分区：
文献类型：
--
作者：
Ponjavic, Jasmina;Lenhard, Boris;Kai, Chikatoshi;Kawai, Jun;Carninci, Piero;Hayashizaki, Yoshihide;Sandelin, Albin
小鼠核心启动子中TATA盒和转录起始位点之间的间隔的研究揭示了间隔与组织特异性的耦合。TATA盒是研究最充分的核心启动子元件之一，与诱导的上下文特异性表达相关。缺乏精确的转录起始位点（TSS）与表达信息的位置，阻碍了TATA和前起始复合物之间的相互作用的全基因组表征。利用一组来自不同组织的5.66 × 106个测序的5' cDNA末端定位到小鼠基因组，我们发现TATA-TSS距离与下游转录物的组织特异性相关。为了实现组织特异性调节，TATA盒相对于TSS的位置被限制在窄窗口（-32至-29），其中位置-31和-30是实现高组织特异性的最佳位置。只有当没有最佳间隔的起始信号时，才能容纳稍大的间隔;相反，在位置-28下游发现的TATA盒样基序通常是无功能的。TATA结合蛋白-DNA相互作用的强度在组织特异性方面起着从属于间隔的作用。此外，具有不同TATA-TSS间距的启动子在起始位点周围的共有序列和备选TSS的分布方面具有不同的特征。出乎意料的是，具有两个显性连续TSS的启动子是TATA耗尽的，并且具有新的GGG起始位点共有序列。在这份报告中，我们提出了最全面的表征TATA-TSS间距和功能的日期。在转录组水平上，间隔与组织特异性的耦合为核心启动子的功能和前起始复合物对TSS的选择提供了重要线索。
Investigations of the spacing between TATA box and transcription start site in mouse core promoters reveals a coupling of spacing to tissue specificity. The TATA box, one of the most well studied core promoter elements, is associated with induced, context-specific expression. The lack of precise transcription start site (TSS) locations linked with expression information has impeded genome-wide characterization of the interaction between TATA and the pre-initiation complex. Using a comprehensive set of 5.66 × 106 sequenced 5' cDNA ends from diverse tissues mapped to the mouse genome, we found that the TATA-TSS distance is correlated with the tissue specificity of the downstream transcript. To achieve tissue-specific regulation, the TATA box position relative to the TSS is constrained to a narrow window (-32 to -29), where positions -31 and -30 are the optimal positions for achieving high tissue specificity. Slightly larger spacings can be accommodated only when there is no optimally spaced initiation signal; in contrast, the TATA box like motifs found downstream of position -28 are generally nonfunctional. The strength of the TATA binding protein-DNA interaction plays a subordinate role to spacing in terms of tissue specificity. Furthermore, promoters with different TATA-TSS spacings have distinct features in terms of consensus sequence around the initiation site and distribution of alternative TSSs. Unexpectedly, promoters that have two dominant, consecutive TSSs are TATA depleted and have a novel GGG initiation site consensus. In this report we present the most comprehensive characterization of TATA-TSS spacing and functionality to date. The coupling of spacing to tissue specificity at the transcriptome level provides important clues as to the function of core promoters and the choice of TSS by the pre-initiation complex.