Gershenzon Naum I, Trifonov Edward N, Ioshikhes Ilya P
Department of Biomedical Informatics, The Ohio State University, 333 West 10th Avenue, Columbus, OH 43210, USA.
BMC Genomics. 2006 Jun 21;7:161. doi: 10.1186/1471-2164-7-161.
Experimental investigation of transcription is still a very labor- and time-consuming process. Only a few transcription initiation scenarios have been studied in detail. The mechanism of interaction between basal machinery and promoter, in particular core promoter elements, is not known for the majority of identified promoters. In this study, we reveal various transcription initiation mechanisms by statistical analysis of 3393 nonredundant Drosophila promoters.
Using Drosophila-specific position-weight matrices, we identified promoters containing TATA box, Initiator, Downstream Promoter Element (DPE), and Motif Ten Element (MTE), as well as core elements discovered in Human (TFIIB Recognition Element (BRE) and Downstream Core Element (DCE)). Promoters utilizing known synergetic combinations of two core elements (TATA_Inr, Inr_MTE, Inr_DPE, and DPE_MTE) were identified. We also establish the existence of promoters with potentially novel synergetic combinations: TATA_DPE and TATA_MTE. Our analysis revealed several motifs with the features of promoter elements, including possible novel core promoter element(s). Comparison of Human and Drosophila showed consistent percentages of promoters with TATA, Inr, DPE, and synergetic combinations thereof, as well as most of the same functional and mutual positions of the core elements. No statistical evidence of MTE utilization in Human was found. Distinct nucleosome positioning in particular promoter classes was revealed.
We present lists of promoters that potentially utilize the aforementioned elements/combinations. The number of these promoters is two orders of magnitude larger than the number of promoters in which transcription initiation was experimentally studied. The sequences are ready to be experimentally tested or used for further statistical analysis. The developed approach may be utilized for other species.
转录的实验研究仍然是一个非常耗费人力和时间的过程。仅有少数转录起始情况得到了详细研究。对于大多数已鉴定的启动子而言，基础机制与启动子之间的相互作用机制，尤其是核心启动子元件的相互作用机制尚不清楚。在本研究中，我们通过对3393个非冗余果蝇启动子进行统计分析，揭示了多种转录起始机制。
利用果蝇特异性位置权重矩阵，我们鉴定出了含有TATA框、起始子、下游启动子元件（DPE）和基序十元件（MTE）的启动子，以及在人类中发现的核心元件（TFIIB识别元件（BRE）和下游核心元件（DCE））。我们还鉴定出了利用两种核心元件（TATA_Inr、Inr_MTE、Inr_DPE和DPE_MTE）已知协同组合的启动子。我们还确定了具有潜在新型协同组合的启动子的存在：TATA_DPE和TATA_MTE。我们的分析揭示了几个具有启动子元件特征的基序，包括可能的新型核心启动子元件。人类和果蝇的比较显示，具有TATA、Inr、DPE及其协同组合的启动子百分比一致，以及核心元件的大多数相同功能和相互位置。在人类中未发现使用MTE的统计证据。揭示了特定启动子类别中不同的核小体定位。
我们列出了可能利用上述元件/组合的启动子清单。这些启动子的数量比通过实验研究转录起始的启动子数量大两个数量级。这些序列随时可用于实验测试或进一步的统计分析。所开发的方法可用于其他物种。
