Figure 5

Two stochastic models for mutually exclusive OR transcription. Transcription factors (small triangles, circles) interact with cis regulatory sequences to generate OR gene loci that are competent for transcription (white versus gray/black rectangles). For example, OR genes might be more or less competent for transcription based on factors that specify geographic zone in the olfactory epithelium. a) Singular OR activating complex. A single transcriptional complex (large black circle) assembles at one physical location in the nucleus (e.g., nuclear structure or "H region"-like sequence in the genome [119, 120]), to which only one competent OR gene can stably associate. This model predicts that only one OR allele is physically able to be transcribed at once. In this model, feedback mechanisms might further stabilize/reinforce an OR-complex interaction or inhibit other OR loci from competing for the complex. b) Epigenetic regulation of OR genes. This model invokes a ground state of repression at OR loci. Deterministic factors specifying spatial or temporal information (small triangles, circles), or associated enhancers such as the "H region", reduce repressive chromatin states, thereby increasing rates of transcription. Because the overall transcriptional rates are nevertheless slow (even in the most activated loci), the likelihood of multiple ORs achieving a super-threshold level of protein expression (dashed line) is reduced. Kinetic profiles representing OR transcript levels over time (t) are shown at the bottom of the figure. Once a single OR achieves a super-threshold level of expression, a feedback inhibition mechanism silences other OR loci (represented by abrupt descent in kinetic profiles). Such a model requires that the selected OR locus be protected from this inhibitory process.