Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell. 2011 May 13;145(4):555-70. doi: 10.1016/j.cell.2011.03.040. Epub 2011 Apr 28.
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.
传统上认为组成型异染色质是异染色质的静态形式，以细胞周期和分化独立的方式沉默着着丝粒和端粒重复序列。在这里，我们表明，在小鼠嗅觉上皮中，嗅觉受体 (OR) 基因以高度动态的方式被标记，具有组成型异染色质的分子特征，即 H3K9me3 和 H4K20me3。这些标记沿着 OR 簇的细胞类型和发育依赖性沉积很可能在 OR 选择过程中被逆转，以允许单基因和单等位基因 OR 表达。与当前的 OR 选择观点相反，我们的数据表明，OR 沉默发生在 OR 表达之前，这表明它不是 OR 引发的反馈信号的产物。我们的发现表明，染色质介导的沉默为基因表达的单一和随机选择奠定了分子基础。
