Promoter architecture of mouse olfactory receptor genes

Abstract

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.

Nuclear compartmentalization of odorant receptor genes

“…It has been clearly demonstrated that OR gene promoters are necessary for OR gene expression (6,7); however, because these promoters show similar cisregulatory elements (8)(9)(10)(11)(12), it is not clear how monogenic OR gene expression is achieved. Previous studies have identified cis-acting enhancers located upstream of OR gene clusters (denominated H and P elements) which can select one single gene for expression (13)(14)(15).…”

Monoallelic Expression of Olfactory Receptors

“…OR promoter sequences are required for the expression of OR transgenes, and an OR promoter is sufficient to drive MOE-specific expression of a reporter transgene (Plessy et al 2012; Rothman et al 2005; Vassalli et al 2002, 2011). These findings suggest that OR promoters contain sequences that are sufficient to recapitulate OR activation.…”

“…Analyses of OR promoters have identified shared regulatory sequences (Clowney et al 2011; Michaloski et al 2006; 2011; Plessy et al 2012; Young et al 2011). These studies have reliably identified O/E family motifs and homeodomain motifs in most OR promoter sequences (Figure 2).…”

Chemosensory Receptor Specificity and Regulation

“…Numerous studies have assayed the structure of OR promoters and proximal regions to identify factors required for OR expression (Michaloski et al 2006, Clowney et al 2011, Plessy et al 2012). A high-throughput analysis of OR promoters revealed a number of striking features.…”

“…OR promoters are enriched for homeodomain sites as well as for O/E (Olf1/early B cell factor)-like sites (Michaloski et al 2006, Clowney et al 2011, Plessy et al 2012). Two homeodomain proteins, LHX2 and EMX2, regulate OR gene expression.…”