Gene mapping reveals architecture that controls expression of genes responsible for our sense of smell

May 18, 2012
Figure 1: An artistic representation of how the nanoCAGE technique flags the gene promoters for the vast majority of mouse olfactory genes. Credit: 2012 Charles Plessy, RIKEN Omics Science Center

Within the nasal cavity, millions of sensory neurons in a postage-stamp-sized patch of tissue called the olfactory epithelium control our sense of smell. Thanks to the exquisitely controlled expression of some 300 different olfactory receptor genes, each neuron can detect a small number of distinct volatile odorants. How these genes are regulated, however, has long been a mystery.

Now, an international team led by RIKEN researchers has mapped the genomic architecture of the odorant receptor repertoire in mice, revealing the start points and promoter regions involved in controlling the expression of the vast majority of these genes. “Our study shows that these promoter sequences are strikingly similar between all the olfactory receptors,” says Charles Plessy of the RIKEN Omics Science Center in Yokohama, who led the study.

To chart all the promoters, Plessy and colleagues first had to devise an appropriate technique. Plessy’s collaborator, Piero Carninci also from the RIKEN Omics Science Center, had previously developed a method called cap-analysis gene expression (CAGE) that determines the location of transcription start sites across the whole genome. But CAGE requires large quantities of RNA, which are not always obtainable from particular types of tissues, including the olfactory epithelium. The researchers therefore modified CAGE to nanoCAGE, which requires as little as 10 nanograms of RNA of biological material per sample.

Both CAGE and nanoCAGE work by taking all the messenger RNA transcripts in a given sample, converting them into DNA tags and then comparing the output against a reference genome to find all the transcription start sites. The investigators can then decipher the conserved DNA regulatory sequences in the immediate vicinity of the starting points that form the core promoters.

Using this approach on the minute quantities of RNA found in the olfactory epithelium of mice, Plessy’s team plotted the promoters of almost 90% of the mouse olfactory receptor genes, as well as the expression of many non-coding regulatory RNAs (Fig. 1). Further bioinformatic analysis of the DNA surrounding the mapped promoters revealed a number of candidate transcription factor binding sites that help control gene expression, some of which the researchers also validated in mouse experiments.

Plessy and colleagues are now adapting the CAGE technique for even smaller biological samples: single cells. “Such a method would have wide applications in biology and medicine, and, of course, in the biology of olfactory receptors,” says Plessy. “With a single-cell technology we will have the potential to make a significant contribution to the field.”

Explore further: NanoCAGE reveals transcriptional landscape of the mouse main olfactory epithelium

More information: Plessy, C., et al. Promoter architecture of mouse olfactory receptor genes. Genome Research advance online publication, 22 December 2011 (doi: 10.1101/gr.126201.111).

Shiraki, T., et al. Cap analysis gene expression for high-throughput analysis of transcriptional starting point and identification of promoter usage. Proceedings of the National Academy of Sciences USA 100, 15776–15781 (2003).

Plessy, C., et al. Linking promoters to functional transcripts in small samples with nanoCAGE and CAGEscan. Nature Methods 7, 528–534 (2010).

Related Stories

NanoCAGE reveals transcriptional landscape of the mouse main olfactory epithelium

January 5, 2012
The problem in biology of how to identify the promoters of olfactory receptor genes (>1000 genes) has remained unsolved due to the difficulty of purifying sufficient material from the olfactory epithelium. Researchers at ...

Gene switch for odorant receptors

November 11, 2011
The olfactory sensory neurons in the nasal mucosa perceive the myriad smells in the air with the aid of odorant receptors. Each sensory neuron chooses one and only one receptor gene for expression. The probability that a ...

Recommended for you

Large genetic study links tendency to undervalue future rewards with ADHD, obesity

December 11, 2017
Researchers at University of California San Diego School of Medicine have found a genetic signature for delay discounting—the tendency to undervalue future rewards—that overlaps with attention-deficit/hyperactivity disorder ...

Gene variants identified that may influence sexual orientation in men and boys

December 8, 2017
(Medical Xpress)—A large team of researchers from several institutions in the U.S. and one each from Australia and the U.K. has found two gene variants that appear to be more prevalent in gay men than straight men, adding ...

Disease caused by reduction of most abundant cellular protein identified

December 8, 2017
An international team of scientists and doctors has identified a new disease that results in low levels of a common protein found inside our cells.

Study finds genetic mutation causes 'vicious cycle' in most common form of amyotrophic lateral sclerosis

December 8, 2017
University of Michigan-led research brings scientists one step closer to understanding the development of neurodegenerative disorders such as ALS.

Mutations in neurons accumulate as we age: The process may explain normal cognitive decline and neurodegeneration

December 7, 2017
Scientists have wondered whether somatic (non-inherited) mutations play a role in aging and brain degeneration, but until recently there was no good technology to test this idea. A study published online today in Science, ...

Researchers find genes may 'snowball' obesity

December 7, 2017
There are nine genes that make you gain more weight if you already have a high body mass index, McMaster University researchers have found.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

JVK
not rated yet May 19, 2012
This suggests to me that adaptation of the CAGE technique for single cells will allow them to detail how nutrient chemicals cause the receptor-mediated changes in intracellular signaling and stochastic gene expression that lead to de novo olfactory receptor gene expression. These are the changes that establish new nutrient dependent ecological niches accompanied by social niches that are standardized and controlled by pheromones. In the honeybee invertebrate model, and stickleback vertebrate model the nutrient chemicals and pheromones control brain development and speciation. Model organisms make clear the extension of the concept to nutrient chemical and pheromone-dependent human brain development and individual differences (especially sex differences) in behavior. So, why is this in the current news when it was first published in December?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.