Computational analysis of core promoters in the Drosophila genome.
Computational analysis of core promoters in the Drosophila genome.
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DOI：
10.1186/gb-2002-3-12-research0087
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发表时间：
2002
期刊：
影响因子：
12.3
通讯作者：
Rubin GM
中科院分区：
文献类型：
--
作者：
Ohler U;Liao GC;Niemann H;Rubin GM
通过将5‘端表达序列标签(EST)与基因组进行比对，已经确定了大约2000个果蝇基因的候选转录起始点。对这些候选转录起始点两侧序列的检测发现，存在众所周知的核心启动子基序，如TATA盒、启动子和下游启动子元件(DPE)。核心启动子位于转录起始点(TSS)两侧，约有100个碱基对，是基础转录装置的识别位点。果蝇的TSS通常是通过个体实验定位的；准确定位的TSS数量较少，限制了对启动子序列基序的分析和计算预测工具的训练。我们通过将帽子捕获的cDNA文库中的5‘表达序列标签(EST)与基因组进行比对，同时采用严格的覆盖率和5’端分布标准，确定了大约2,000个果蝇基因的TSS候选基因。对这些TSS两侧序列的检测显示，存在众所周知的核心启动子基序，如TATA盒、启动子和下游启动子元件(DPE)。我们还定义并评估了在核心启动子中流行的几个新基序的分布，包括似乎是变异的DPE基序。在流行的基序中，有DNA复制相关元件Dre，最近被证明是TBP相关因子TRF2识别位点的一部分。然后使用我们的TSS集重新训练计算启动子预测McPromoter，使我们能够将识别性能提高到50%以上的灵敏度和40%的特异度。我们将这些计算结果与脊椎动物中的启动子预测进行了比较。在果蝇核心启动子中，已知的一般转录因子的可识别结合位点相对较少。然而，我们发现了几个新的富含在启动子区域的基序。我们还能够显著提高果蝇计算TSS预测的性能。
Candidate transcription start sites have been identified for about 2,000 Drosophila genes by aligning 5' expressed sequence tags (ESTs) from cap-trapped cDNA libraries to the genome. Examination of the sequences flanking these candidate transcription start sites revealed the presence of well-known core promoter motifs such as the TATA box, the initiator and the downstream promoter element (DPE). The core promoter, a region of about 100 base-pairs flanking the transcription start site (TSS), serves as the recognition site for the basal transcription apparatus. Drosophila TSSs have generally been mapped by individual experiments; the low number of accurately mapped TSSs has limited analysis of promoter sequence motifs and the training of computational prediction tools. We identified TSS candidates for about 2,000 Drosophila genes by aligning 5' expressed sequence tags (ESTs) from cap-trapped cDNA libraries to the genome, while applying stringent criteria concerning coverage and 5'-end distribution. Examination of the sequences flanking these TSSs revealed the presence of well-known core promoter motifs such as the TATA box, the initiator and the downstream promoter element (DPE). We also define, and assess the distribution of, several new motifs prevalent in core promoters, including what appears to be a variant DPE motif. Among the prevalent motifs is the DNA-replication-related element DRE, recently shown to be part of the recognition site for the TBP-related factor TRF2. Our TSS set was then used to retrain the computational promoter predictor McPromoter, allowing us to improve the recognition performance to over 50% sensitivity and 40% specificity. We compare these computational results to promoter prediction in vertebrates. There are relatively few recognizable binding sites for previously known general transcription factors in Drosophila core promoters. However, we identified several new motifs enriched in promoter regions. We were also able to significantly improve the performance of computational TSS prediction in Drosophila.