An Epigenetic Signature for Monoallelic Olfactory Receptor Expression

Constitutive heterochromatin is traditionally viewed as the static form of heterochromatin that silences pericentromeric and telomeric repeats in a cell cycle- and differentiation-independent manner. Here, we show that, in the mouse olfactory epithelium, olfactory receptor (OR) genes are marked in a highly dynamic fashion with the molecular hallmarks of constitutive heterochromatin, H3K9me3 and H4K20me3. The cell type and developmentally dependent deposition of these marks along the OR clusters are, most likely, reversed during the process of OR choice to allow for monogenic and monoallelic OR expression. In contrast to the current view of OR choice, our data suggest that OR silencing takes place before OR expression, indicating that it is not the product of an OR-elicited feedback signal. Our findings suggest that chromatin-mediated silencing lays a molecular foundation upon which singular and stochastic selection for gene expression can be applied. [Display omitted] ► OR genes are repressed via H3K9me2 in stem cells of the olfactory epithelium ► During differentiation, OR silencing is mediated by the trimethylation of H3K9 and H4K20 ► H3K9 and H4K20 likely get demethylated at a single OR allele during OR choice ► This epigenetic system induces OR-like expression on an heterologous promoter