title: Functional interrogation of an odorant receptor locus reveals multiple axes of transcriptional regulation.
abstract: 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.
authors.affiliation: Center for Interdisciplinary Research in Biology, College de France, Paris, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Fleischmann
authors.forename: Ishmail
authors.initials: I
authors.lastname: Abdus-Saboor
authors.forename: Atef
authors.initials: A
authors.lastname: Sayed
authors.forename: Benjamin
authors.initials: B
authors.lastname: Shykind
mesh_terms: D000483:Alleles; D000818:Animals; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D018035:Receptors, Odorant / Q000235:genetics*; D013752:Tetracycline; D015533:Transcriptional Activation; D019076:Transgenes
chemical_list: D018035:Receptors, Odorant; D013752:Tetracycline