An Epigenetic Signature for Monoallelic Olfactory Receptor Expression

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell (Impact Factor: 33.12). 05/2011; 145(4):555-70. DOI: 10.1016/j.cell.2011.03.040
Source: PubMed

ABSTRACT 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.

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Available from: Gilad Barnea, Apr 22, 2014
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    • "In the mammalian central nervous system, each olfactory sensory neuron expresses only one olfactory receptor (OR) from a family of ∼1200 genes (Buck and Axel, 1991). Before an OR gene is expressed, all alleles are silenced and converted to heterochromatin (Magklara et al., 2011). A limiting enzymatic activity then stochastically removes the heterochromatin marks from one allele to activate it. "
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    • "Virtually nothing is understood about the establishment of MAE during development and differentiation. Mechanistically, allelic choice has been linked to changes in chromatin states in some special cases: imprinting (Wen et al., 2008), olfactory receptor gene choice (Magklara et al., 2011), and immunoglobulin-kappa gene rearrangement (Farago et al., 2012). In contrast, for hundreds of other autosomal MAE genes, no molecular features have been associated with establishment and maintenance of allelic choice. "
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