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Commonality of Odorant Receptor Choice Mechanism Revealed by Analysis of a Highly Represented Odorant Receptor Transgene

ABSTRACT: Commonality of Odorant Receptor Choice Mechanism Revealed by Analysis of a Highly Represented Odorant Receptor Transgene

PROVIDER: PRJNA856389 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20011663.fastq.gz	Fastqsanger.gz
	SRR20011664.fastq.gz	Fastqsanger.gz
	SRR20011665.fastq.gz	Fastqsanger.gz
	SRR20011666.fastq.gz	Fastqsanger.gz
	SRR20011667.fastq.gz	Fastqsanger.gz

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Commonality of Odorant Receptor Choice Mechanism Revealed by Analysis of a Highly Represented Odorant Receptor Transgene

Project description:In the mouse, more than 1,100 odorant receptors (ORs) are expressed in a monogenic and monoallelic fashion, referred to as singular gene expression. Using a 21bp singular-choice enhancer (x21), we radically increase representation of olfactory sensory neurons (OSNs) choosing a 5×21 enhanced OR transgene, but not overexpression of its mRNA on a per cell basis. RNA-sequencing and differential expression analysis identified 425 differentially expressed genes (DEGs). ORs make up 86% of all DEGs, of which 325 have decreased representation and 40 have increased representation. Underrepresented ORs include Class I, Class II and TAAR genes and within each of their respective olfactory bulb domains: DI, DII, and DIII (TAAR) we committedly observe multiple homogeneous glomeruli with an OR1A1-identity. The underrepresentation of endogenous, class-specific ORs across evolutionarily distinct cell types in favor of the expression of the 5×21-OR1A1 transgene argues that a common mechanism of singular gene choice is present for all OR-expressing OSNs

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A Common Mechanism of Singular Gene Choice is Revealed by Broadly Expressed Odorant Receptor Transgenes within the Olfactory Epithelium

Project description:In the mouse, more than 1,100 odorant receptors (ORs) are expressed in a monogenic and monoallelic fashion, referred to as singular gene expression. Here we utilize multimers of a naturally occurring 21bp enhancer (x21) and radically increase the number of olfactory sensory neurons (OSNs) choosing an OR transgene that is normally expressed by Class II cell types. Surprisingly, hundreds of ORs derived from Class I, Class II and TAAR cell types have reduced expression and are replaced by the OR transgene expression leading to novel glomeruli formed in three segregating domains of glomeruli on the olfactory bulb: DI (Class I), DII (Class II), and DIII (TAAR). The reduction of expression across distinct cell types that were thought to have distinct mechanisms of singular gene choice in favor of the expression of the x21-OR transgene argues that a common mechanism of singular gene choice is present for all OR-expressing OSNs.

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Silencing of odorant receptor gene expression by G protein M-NM-2M-NM-3 signaling ensures the expression of one odorant receptor per olfactory sensory neuron

Project description: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 M-NM-2M-NM-3 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. Total 6 samples were analyzed-3 controls & 3 samples

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