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

Todd Ferreira; Sarah R Wilson; Yoon Gi Choi; Davide Risso; Sandrine Dudoit; Terence P Speed; John Ngai

doi:10.1016/j.neuron.2014.01.001

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

Neuron. 2014 Feb 19;81(4):847-59. doi: 10.1016/j.neuron.2014.01.001.

Authors

Todd Ferreira¹, Sarah R Wilson¹, Yoon Gi Choi², Davide Risso³, Sandrine Dudoit⁴, Terence P Speed⁵, John Ngai⁶

Affiliations

¹ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
² Functional Genomics Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA.
³ Department of Statistics, University of California, Berkeley, Berkeley, CA 94720, USA.
⁴ Division of Biostatistics, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Statistics, University of California, Berkeley, Berkeley, CA 94720, USA.
⁵ Department of Statistics, University of California, Berkeley, Berkeley, CA 94720, USA; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville VIC 3050, Australia.
⁶ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Functional Genomics Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: jngai@berkeley.edu.

Abstract

Olfactory sensory neurons express just one out of a possible ∼ 1,000 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 link receptor activity with the epigenetic mechanisms responsible for ensuring the expression of one odorant receptor per olfactory sensory neuron.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Axons / metabolism
GTP-Binding Protein beta Subunits / metabolism*
GTP-Binding Protein gamma Subunits / metabolism*
Gene Expression Regulation, Developmental / genetics
Gene Expression Regulation, Developmental / physiology
Olfactory Bulb / metabolism*
Olfactory Receptor Neurons / metabolism*
Receptors, Odorant / genetics
Receptors, Odorant / metabolism*
Sensory Receptor Cells / metabolism*
Signal Transduction / genetics*
Zebrafish / metabolism*

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

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