Functional Interrogation of an Odorant Receptor Locus Reveals Multiple Axes of Transcriptional Regulation

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 (teto),we observed that the or locus imposes spatial and temporal constraints on teto-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 teto. neurons homozygous for the teto-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. © 2013 fleischmann et al.