V1R promoters are well conserved and exhibit common putative regulatory motifs.
V1R promoters are well conserved and exhibit common putative regulatory motifs.
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V1R启动子是保守的，并且具有常见的推定调节基序。
DOI：
10.1186/1471-2164-8-253
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发表时间：
2007-07-25
期刊：
影响因子：
4.4
通讯作者：
Lane, Robert P
中科院分区：
文献类型：
--
作者：
Stewart, Robert;Lane, Robert P
小鼠犁鼻器官（VNO）处理化学感觉信息，包括影响生殖行为的信息素信号。VNO的感觉神经元表达两种化学感觉受体V1R和V2R。小鼠基因组中有大约165个V1R基因，被分为大约12个不同的亚家族。VNO顶端室的每个感觉神经元只转录V1R基因中的一个。提出了这些细胞中互斥V1R转录的模型，其中每个V1R基因可能随机竞争单个转录复合体。该模型预测，小鼠基因组中大量不同的V1R基因包含共同的调控元件。在这项研究中，我们通过比较基因组学和转录起始位点的定位来表征V1R启动子区域。我们发现转录是从约1kb的启动子区域开始的，这些启动子区域在V1R亚家族中很保守。虽然传统方法无法发现跨亚家族同源性，但我们开发了启发式基序搜索工具LogoAlign，并应用该工具识别所有V1R基因启动子内共享的基序。我们的主题搜索工具显示出对相对少量的非冗余解的快速收敛（97%收敛）。我们还发现，与对照组相比，最佳基序包含更多的信息，并且这些基序更有可能出现在转录起始位点附近，而不是基因块中的其他地方。最好的基序出现在约90%的V1R基因的转录起始位点附近，并跨越所有不同的亚家族。因此，这些基序是参与V1R共调控的转录因子的候选结合位点。我们的分析表明，V1R亚家族具有广泛且保守的启动子区域，从该区域开始转录。一种新的基序查找算法LogoAlign的结果表明，存在着共同的信息丰富的调控基序，这些基序在不同的V1R亚族中是共享的。LogoAlign是为这种情况而设计的，更广泛地用于搜索大型分层数据集。
The mouse vomeronasal organ (VNO) processes chemosensory information, including pheromone signals that influence reproductive behaviors. The sensory neurons of the VNO express two types of chemosensory receptors, V1R and V2R. There are ~165 V1R genes in the mouse genome that have been classified into ~12 divergent subfamilies. Each sensory neuron of the apical compartment of the VNO transcribes only one of the repertoire of V1R genes. A model for mutually exclusive V1R transcription in these cells has been proposed in which each V1R gene might compete stochastically for a single transcriptional complex. This model predicts that the large repertoire of divergent V1R genes in the mouse genome contains common regulatory elements. In this study, we have characterized V1R promoter regions by comparative genomics and by mapping transcription start sites. We find that transcription is initiated from ~1 kb promoter regions that are well conserved within V1R subfamilies. While cross-subfamily homology is not evident by traditional methods, we developed a heuristic motif-searching tool, LogoAlign, and applied this tool to identify motifs shared within the promoters of all V1R genes. Our motif-searching tool exhibits rapid convergence to a relatively small number of non-redundant solutions (97% convergence). We also find that the best motifs contain significantly more information than those identified in controls, and that these motifs are more likely to be found in the immediate vicinity of transcription start sites than elsewhere in gene blocks. The best motifs occur near transcription start sites of ~90% of all V1R genes and across all of the divergent subfamilies. Therefore, these motifs are candidate binding sites for transcription factors involved in V1R co-regulation. Our analyses show that V1R subfamilies have broad and well conserved promoter regions from which transcription is initiated. Results from a new motif-finding algorithm, LogoAlign, designed for this context and more generally for searching large, hierarchical datasets, suggest the existence of common information-rich regulatory motifs that are shared across otherwise divergent V1R subfamilies.