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An epigenetic signature for monoallelic olfactory receptor expression
Authors:Magklara Angeliki  Yen Angela  Colquitt Bradley M  Clowney E Josephine  Allen William  Markenscoff-Papadimitriou Eirene  Evans Zoe A  Kheradpour Pouya  Mountoufaris George  Carey Catriona  Barnea Gilad  Kellis Manolis  Lomvardas Stavros
Affiliation:1 Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA
2 Program in Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA
3 Program in Biomedical Sciences, University of California, San Francisco, San Francisco, CA 94158, USA
4 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
5 Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA
6 Department of Neuroscience, Brown University, Providence, RI 02912, USA
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.
Keywords:
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