LDSS-P: an advanced algorithm to extract functional short motifs associated with coordinated gene expression.
LDSS-P: an advanced algorithm to extract functional short motifs associated with coordinated gene expression.
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DOI：
10.1093/nar/gkw435
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发表时间：
2016-06-20
影响因子：
14.9
通讯作者：
Long SR
中科院分区：
文献类型：
--
作者：
Ichida H;Long SR
识别启动子序列中的功能元件是计算和实验基因组生物学的一个主要目标。在这里，我们描述了一种算法，原核生物短序列局部分布（LDSS-P），用于识别位于共表达原核基因启动子特定位置的保守短基序。作为测试案例，我们将该算法应用于共生固氮细菌苜蓿中华根瘤菌。与胞质外功能 RNA 聚合酶 σ 因子 RpoE2 共有序列的 5' 部分重叠的 LDSS-P 谱在 TSS 位置的 -34 和 -32 之间显示出尖峰。相应的基因与之前实验中确定的 RpoE2 靶标显着重叠。我们进一步鉴定了几组与特征标记基因共同调控的基因。我们的数据表明，在苜蓿中华根瘤菌中，也可能在其他根瘤菌科物种中，主细胞周期调节因子 CtrA 可能识别一个扩展基序 (AACCAT)，该基序与先前报道的新月柄杆菌中的 CtrA 共有序列发生位置偏移。细菌单杂交实验表明，扩展基序中的碱基取代会增加或减少 CtrA 的结合。这些结果表明 LDSS-P 作为描述功能启动子元件的方法的有效性。
Identifying functional elements in promoter sequences is a major goal in computational and experimental genome biology. Here, we describe an algorithm, Local Distribution of Short Sequences for Prokaryotes (LDSS-P), to identify conserved short motifs located at specific positions in the promoters of co-expressed prokaryotic genes. As a test case, we applied this algorithm to a symbiotic nitrogen-fixing bacterium, Sinorhizobium meliloti. The LDSS-P profiles that overlap with the 5′ section of the extracytoplasmic function RNA polymerase sigma factor RpoE2 consensus sequences displayed a sharp peak between -34 and -32 from TSS positions. The corresponding genes overlap significantly with RpoE2 targets identified from previous experiments. We further identified several groups of genes that are co-regulated with characterized marker genes. Our data indicate that in S. meliloti, and possibly in other Rhizobiaceae species, the master cell cycle regulator CtrA may recognize an expanded motif (AACCAT), which is positionally shifted from the previously reported CtrA consensus sequence in Caulobacter crescentus. Bacterial one-hybrid experiments showed that base substitution in the expanded motif either increase or decrease the binding by CtrA. These results show the effectiveness of LDSS-P as a method to delineate functional promoter elements.