Silencing of Odorant Receptor Genes by G Protein βγ Signaling Ensures the Expression of One Odorant Receptor per Olfactory Sensory Neuron

Abstract

Summary Olfactory sensory neurons express just one out of a possible ~1000 odorant receptor genes, reflecting an exquisite mode of gene regulation. In one model, once an odorant receptor is chosen for expression, other receptor genes are suppressed by a negative feedback mechanism, ensuring a stable functional identity of the sensory neuron for the lifetime of the cell. The signal transduction mechanism subserving odorant receptor gene silencing remains obscure, however. Here we demonstrate in the zebrafish that odorant receptor gene silencing is dependent on receptor activity. Moreover, we show that signaling through G protein βγ subunits is both necessary and sufficient to suppress the expression of odorant receptor genes, and likely acts through histone methylation to maintain the silenced odorant receptor genes in transcriptionally inactive heterochromatin. These results provide new insights linking receptor activity with the epigenetic mechanisms responsible for ensuring the expression of one odorant receptor per olfactory sensory neuron.

Heterochromatin-Mediated Gene Silencing Facilitates the Diversification of Olfactory Neurons

“…In this note, our data, with the exemption of the few upregulated ORs, diverge from recent observations in zebrafish OSNs, whereby pharmacological inhibition of G9a/Glp results in increased frequency of OR co-expression (Ferreira et al, 2014). Although in zebrafish embryos the global effects of G9a/Glp inhibition on OR transcription were not determined, inhibition of G9a/Glp caused robust OR co-expression for several ORs analyzed by two-color RNA FISH, suggesting that de-silencing is sufficient for robust OR expression in this organism.…”

“…However, recent theoretical models suggest that singular OR expression could also be explained just by a combination of a slow H3K9 demethylation process and a fast feedback that blocks further demethylation(Tan et al, 2013). In this scenario, removal of the repressive histone marks from a randomly chosen OR allele could be essential and sufficient for OR expression, a hypothesis supported by pharmacological inhibition of G9a/GLP in zebrafish embryos(Ferreira et al, 2014). …”

Enhancer Interaction Networks as a Means for Singular Olfactory Receptor Expression

“…The continuous transcription of a single OR is maintained by an OR-elicited feedback signal that stabilizes the expression of the chosen OR and prevents the activation of additional ones (Ferreira et al, 2014; Lewcock and Reed, 2004; Serizawa et al, 2003; Shykind et al, 2004). In mammals, this feedback uses components of the unfolded protein response (UPR) to detect the newly translated OR in the endoplasmic reticulum and to induce transient translation of transcription factor Atf5 (Dalton et al, 2013).…”

svaseq: removing batch effects and other unwanted noise from sequencing data

“…I use data from Zebrafish sensory neurons with three control samples and three gallein treated samples as the comparison groups [21]. These data are available as part of the zebrafishRNAseq Bioconductor package.…”