First Author | Fleischmann A | Year | 2013 |
Journal | PLoS Biol | Volume | 11 |
Issue | 5 | Pages | e1001568 |
PubMed ID | 23700388 | Mgi Jnum | J:201434 |
Mgi Id | MGI:5514102 | Doi | 10.1371/journal.pbio.1001568 |
Citation | Fleischmann A, et al. (2013) Functional interrogation of an odorant receptor locus reveals multiple axes of transcriptional regulation. PLoS Biol 11(5):e1001568 |
abstractText | 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. |