Before revision:  Through constructing and analyzing a mathematical model based on extensive experimental observations , we identified an evolutionarily optimized three-layer regulation mechanism that robustly generates single-allele expression. Zonal separation reduces the number of competing alleles. Bifunctional LSD1 and cooperative histone modification dynamics minimize multiple allele epigenetic activation and alleles trapped in incomplete epigenetic activation states. Subsequent allele competition for a limited number of enhancers through cooperative binding serves as final safeguard for single allele expression.
After revision:  Through constructing and analyzing a mathematical model based on extensive experimental observations , we identified an evolutionarily optimized three-layer regulation mechanism , which includes zonal segregation, epigenetic barrier crossing coupled to a negative feedback loop that mechanistically differs from previous theoretical proposals, and a novel enhancer competition step. This model not only recapitulates monoallelic OR expression, but also elucidates how the olfactory system maximizes and maintains the diversity of OR expression.