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首页> 美国卫生研究院文献>Nucleus >Sequestration within nuclear chromocenters is not a requirement for silencing olfactory receptor transcription in a placode-derived cell line
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Sequestration within nuclear chromocenters is not a requirement for silencing olfactory receptor transcription in a placode-derived cell line

机译：沉默在色浆来源的细胞系中不需要嗅觉受体转录

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摘要

Mouse olfaction depends on specialized olfactory sensory neurons (OSNs) that each express only one olfactory receptor protein from among a family of >1000 olfactory receptor (OR) genes encoded in the genome. To investigate epigenetic mechanisms underlying monogenic OR expression, we characterized the nuclear organization of OR loci in an olfactory placode-derived cell line (OP6) derived from a pre-neuronal cell along the OSN lineage. OR loci are significantly enriched within nuclear chromocenters in these cells as compared with control loci tested. However, we observe variability in chromocenter occupancy among different OR loci and from cell-to-cell, suggesting that these associations are transient or context dependent. The lamin B receptor (LBR), whose downregulation is necessary for aggregation of chromocenters and OR genes in mature OSNs, exhibits an unusual non-peripheral expression pattern in OP6 nuclei; upon further OP6 cell differentiation, LBR expression is lost and chromocenters begin to aggregate. However, neither undifferentiated nor differentiated OP6 cells sequester OR genes within the chromocenters, despite the establishment of monogenic OR expression in these cells. These results indicate that sequestration of competing OR loci is not a requirement for monogenic OR expression in OP6 cells, and could indicate that the initial establishment of monogenic OR expression during OSN differentiation in vivo occurs prior to recruitment of OR genes into chromocenters.
机译：小鼠嗅觉依赖于专门的嗅觉感觉神经元（OSN），它们各自仅表达基因组中编码的> 1000个嗅觉受体（OR）基因家族中的一个嗅觉受体蛋白。为了研究基于单基因OR表达的表观遗传机制，我们表征了沿OSN谱系从前神经元细胞衍生的嗅觉斑母细胞衍生细胞系（OP6）中OR基因座的核组织。与测试的对照基因座相比，OR基因座在这些细胞的核色中心内显着富集。但是，我们观察到不同OR位点之间以及细胞与细胞之间的色心中心占有率存在差异，这表明这些关联是瞬时的或上下文相关的。 Lamin B受体（LBR）的下调对于成熟OSN中的色中心和OR基因的聚集是必需的，在OP6核中表现出异常的非外围表达模式；在进一步OP6细胞分化后，LBR表达消失，色中心开始聚集。然而，尽管在这些细胞中建立了单基因OR表达，但未分化或分化的OP6细胞都没有在色中心内螯合OR基因。这些结果表明，竞争性OR基因座的隔离不是OP6细胞中单基因OR表达的必要条件，并且可能表明OSN体内分化过程中单基因OR表达的最初建立是在OR基因募集入色中心之前发生的。

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