RIKEN Yokohama Institute, Omics Science Center, Yokohama, Kanagawa, Japan.
Genome Res. 2012 Mar;22(3):486-97. doi: 10.1101/gr.126201.111. Epub 2011 Dec 22.
Odorous chemicals are detected by the mouse main olfactory epithelium (MOE) by about 1100 types of olfactory receptors (OR) expressed by olfactory sensory neurons (OSNs). Each mature OSN is thought to express only one allele of a single OR gene. Major impediments to understand the transcriptional control of OR gene expression are the lack of a proper characterization of OR transcription start sites (TSSs) and promoters, and of regulatory transcripts at OR loci. We have applied the nanoCAGE technology to profile the transcriptome and the active promoters in the MOE. nanoCAGE analysis revealed the map and architecture of promoters for 87.5% of the mouse OR genes, as well as the expression of many novel noncoding RNAs including antisense transcripts. We identified candidate transcription factors for OR gene expression and among them confirmed by chromatin immunoprecipitation the binding of TBP, EBF1 (OLF1), and MEF2A to OR promoters. Finally, we showed that a short genomic fragment flanking the major TSS of the OR gene Olfr160 (M72) can drive OSN-specific expression in transgenic mice.
气味化学物质由约 1100 种嗅觉受体 (OR) 检测，这些 OR 由嗅觉感觉神经元 (OSN) 表达。每个成熟的 OSN 被认为只表达单一 OR 基因的一个等位基因。理解 OR 基因表达的转录调控的主要障碍是缺乏对 OR 转录起始位点 (TSS) 和启动子以及 OR 基因座的调节转录本的适当表征。我们已经应用了 nanoCAGE 技术来描绘 MOE 中的转录组和活性启动子。nanoCAGE 分析揭示了 87.5%的小鼠 OR 基因的启动子图谱和结构，以及许多新的非编码 RNA 的表达，包括反义转录本。我们确定了 OR 基因表达的候选转录因子，其中通过染色质免疫沉淀证实 TBP、EBF1 (OLF1) 和 MEF2A 与 OR 启动子结合。最后，我们表明，OR 基因 Olfr160 (M72) 的主要 TSS 侧翼的一小段基因组片段可以在转基因小鼠中驱动 OSN 特异性表达。
