Journal
PLOS BIOLOGY
Volume 11, Issue 5, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.1001568
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Funding
- Qatar National Research Fund (QNRF) [NPRP 09-1011-3-260]
- Biomedical Research Program (BMRP) funds at Weill Cornell Medical College in Qatar, from the Qatar Foundation
- Marie Curie International Reintegration Grant
- Fondation pour la Recherche Medical
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The odorant receptor (OR) genes constitute the largest mammalian gene family and are expressed in a monogenic and monoallelic fashion, through an unknown mechanism that likely exploits positive and negative regulation. We devised a genetic strategy in mice to examine OR selection by determining the transcriptional activity of an exogenous promoter homologously integrated into an OR locus. Using the tetracycline-dependent transactivator responsive promoter (tet(o)), we observed that the OR locus imposes spatial and temporal constraints on tet(o)-driven transcription. Conditional expression experiments reveal a developmental change in the permissiveness of the locus. Further, expression of an OR transgene that suppresses endogenous ORs similarly represses the OR-integrated tet(o). Neurons homozygous for the tet(o)-modified allele demonstrate predominantly monoallelic expression, despite their potential to express both copies. These data reveal multiple axes of regulation, and support a model of initiation of OR choice limited by nonpermissive chromatin and maintained by repression of nonselected alleles.
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