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Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons Depends on Lhx2

ABSTRACT: Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons Depends on Lhx2

PROVIDER: PRJNA300649 | ENA |

REPOSITORIES: ENA

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Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons Depends on Lhx2 [123Cre:Lhx2]

Project description:Conditional deletion of Lhx2, and to a lesser extent, Emx2 in olfactory neurons alters odorant receptor expression frequency. GeneChip microarrays were used to measure odorant receptor mRNAs and test whether their abundance was affected in knockout mice

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Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons Depends on Lhx2 [OmpCre:Lhx2]

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Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons Depends Lhx2 [OmpCre:Emx2]

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Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons Depends on Lhx2

Project description:This SuperSeries is composed of the SubSeries listed below.

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Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons.

Project description:A developmental program of epigenetic repression prepares each mammalian olfactory sensory neuron (OSN) to strongly express one allele from just one of hundreds of odorant receptor (OR) genes, but what completes this process of OR gene choice by driving the expression of this allele is incompletely understood. Conditional deletion experiments in mice demonstrate that Lhx2 is necessary for normal expression frequencies of nearly all ORs and all trace amine-associated receptors, irrespective of whether the deletion of Lhx2 is initiated in immature or mature OSNs. Given previous evidence that Lhx2 binds OR gene control elements, these findings indicate that Lhx2 is directly involved in driving OR expression. The data also support the conclusion that OR expression is necessary to allow immature OSNs to complete differentiation and become mature. In contrast to the robust effects of conditional deletion of Lhx2, the loss of Emx2 has much smaller effects and more often causes increased expression frequencies. Lhx2:Emx2 double mutants show opposing effects on Olfr15 expression that reveal independent effects of these two transcription factors. While Lhx2 is necessary for OR expression that supports OR gene choice, Emx2 can act differently; perhaps by helping to control the availability of OR genes for expression.

| S-EPMC5086798 | biostudies-literature

Chromatin State and Binding of Lhx2 and Ebf in Olfactory Sensory Neurons

Project description:The monoallelic expression of olfactory receptor (OR) genes is governed by the formation of large domain of heterochromatin over OR clusters and by enhancer elements embedded within these heterochromatic domains. Here we show that OR enhancers are bound by Ebf and Lhx2 in mature olfactory sensory neurons (OSNs), and that in the same cell population these sites are flanked by a histone modification characteristic of active enhancers (H3K7ac) as well as modifications characteristic of heterochromatin (H3K9me3 and H3K79me3). We use ATAC-Seq to show that the pattern of OR enhancer accessibility in subpopulations of mOSNs that express a specific OR gene is very similar to the pattern in mOSNs as a whole. Finally, we perturb Ebf and Lhx2 in mOSNs by conditionally deleting Lhx2 or by expressing an Ebf-Lhx2 fusion protein. We profile the effect of these perturbations on OR gene expression by RNA-seq and on chromatin state by ChIP-Seq and ATAC-Seq.

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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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Silencing of odorant receptor gene expression by G protein βγ signaling ensures the expression of one odorant receptor per olfactory sensory neuron

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2013-12-16 | GSE53334 | GEO

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