Abstract
There are more than 1000 odorant receptor (OR) genes in the mouse genome. Each olfactory sensory neuron expresses only one of these genes, in a monoallelic fashion. The transcript abundance of homologous OR genes vary between distinct mouse strains. Here we analyzed the expression of the OR gene Olfr17 (also named P2) in different genomic contexts. Olfr17 is expressed at higher levels in the olfactory epithelium from 129 mice than from C57BL/6 (B6) mice. However, we found that in P2-IRES-tauGFP knock-in mice, the transcript levels of the 129 Olfr17 allele are highly reduced when compared to the B6 Olfr17 allele. To address the mechanisms involved in this variation we compared the 5′ region sequence and DNA methylation patterns of the B6 and 129 Olfr17 alleles. Our results show that genetic variations in cis regulatory regions can lead to differential DNA methylation frequencies in these OR gene alleles. They also show that expression of the Olfr17 alleles is largely affected by the genetic background, and suggest that in knock-in mice, expression can be affected by epigenetic modifications in the region of the targeted locus.
Highlights
Odorants are detected by a large family of odorant receptors (ORs) expressed in the olfactory sensory neurons of the nose (Buck and Axel, 1991)
These results are in agreement with previous RNA-seq experiments, where the transcriptional profiles of the complete OR repertoire was quantified in different mouse strains (Ibarra-Soria et al, 2017)
In the olfactory epithelium from P2-IREStauGFP knock-in (P2-GFP)+/+ mice, Olfr17 is expressed only from 129 alleles, and the Olfr17 transcript levels are significantly reduced when compared to the levels of the olfactory epithelium from P2-GFP−/− mice, where the Olfr17 is expressed from the B6 alleles (Figure 1B)
Summary
Odorants are detected by a large family of odorant receptors (ORs) expressed in the olfactory sensory neurons of the nose (Buck and Axel, 1991). OR gene promoter regions and enhancer sequences are enriched in binding motifs for homeodomain and O/E-like transcription factors (Vassalli et al, 2002; Rothman et al, 2005; Hoppe et al, 2006; Michaloski et al, 2006; Hirota et al, 2007; Nishizumi et al, 2007; Young et al, 2011; Cichy et al, 2019) and motifs for other types of transcription factors (Clowney et al, 2011; Michaloski et al, 2011; Markenscoff-Papadimitriou et al, 2014; Iwata et al, 2017) These motifs are thought to influence OR gene expression frequency in olfactory sensory neurons (Michaloski et al, 2006; Khan et al, 2011; Vassalli et al, 2011; Plessy et al, 2012; Zhang et al, 2016). We found that the transcript levels of other OR genes that are in cis and close to the targeted locus, are reduced in the P2-GFP mice
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
