title: Silencing of odorant receptor genes by G protein βγ signaling ensures the expression of one odorant receptor per olfactory sensory neuron.
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.
authors.affiliation: 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.
authors.forename: Todd
authors.initials: T
authors.lastname: Ferreira
authors.affiliation: 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.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Wilson
authors.affiliation: Functional Genomics Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Yoon Gi
authors.initials: YG
authors.lastname: Choi
authors.affiliation: Department of Statistics, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Davide
authors.initials: D
authors.lastname: Risso
authors.affiliation: Division of Biostatistics, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Statistics, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dudoit
authors.affiliation: 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.
authors.forename: Terence P
authors.initials: TP
authors.lastname: Speed
authors.affiliation: 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.
authors.forename: John
authors.initials: J
authors.lastname: Ngai
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D009830:Olfactory Bulb / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D015027:Zebrafish / Q000378:metabolism*
chemical_list: C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D018035:Receptors, Odorant