Promoter architecture of mouse olfactory receptor genes

Charles Plessy, Giovanni Pascarella, Nicolas Bertin, Altuna Akalin, Claudia Carrieri, Anne Vassalli, Dejan Lazarevic, Jessica Severin, Christina Vlachouli, Roberto Simone, Geoffrey J. Faulkner, Jun Kawai, Carsten O. Daub, Silvia Zucchelli, Yoshihide Hayashizaki, Peter Mombaerts, Boris Lenhard, Stefano Gustincich, Piero Carninci

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.