Function of the mammalian olfactory system depends on specialized olfactory sensory neurons (OSNs) that each express only one allele ("monoallelic") of one odorant receptor (OR) gene ("monogenic"). The lysine-specific demethylase-1 (LSD1) protein removes activating H3K4 or silencing H3K9 methylation marks in a variety of developmental contexts, and is thought to be important for proper OR regulation. Most of the focus in the field has been on a potential "activating" function for LSD1; e.g., in the demethylation of H3K9 associated with the expressed OR allele. Here we show that depletion of LSD1 in an immortalized olfactory-placode-derived cell line (OP6) results in multigenic and multiallelic OR transcription per cell, while not seemingly disrupting the ability of these cells to activate new OR genes during clonal expansion. These results are consistent with LSD1 having a role in silencing additional OR alleles, as opposed to being required for the activation of OR alleles, within the OP6 cellular context.

中文翻译：

---

赖氨酸特异性脱甲基酶-1（LSD1）耗竭破坏嗅觉神经元细胞系中的单基因和单等位气味受体（OR）的表达。

哺乳动物嗅觉系统的功能取决于专门的嗅觉感觉神经元（OSN），每个嗅觉神经元仅表达一种气味受体（OR）基因（“单基因”）的一个等位基因（“单等位基因”）。赖氨酸特异的脱甲基酶-1（LSD1）蛋白在多种发育情况下均会去除活化的H3K4或使H3K9甲基化标记沉默，并且被认为对适当的OR调节很重要。该领域的大多数关注点都集中在LSD1的潜在“激活”功能上。例如，在与表达的OR等位基因相关的H3K9的去甲基化中。在这里，我们显示，永生化的嗅觉基质衍生的细胞系（OP6）中的LSD1耗竭会导致每个细胞的多基因和多等位基因OR转录，而在克隆扩增过程中似乎并没有破坏这些细胞激活新的OR基因的能力。这些结果与LSD1在OP6细胞环境中具有沉默其他OR等位基因的作用相一致，这与激活OR等位基因所需的相反。