Department of Biological Sciences, Universidade Federal São Paulo - UNIFESP, Diadema, Brazil.
Universidade Cidade de São Paulo - UNICID, São Paulo, Brazil.
Mol Cell Neurosci. 2020 Jun;105:103494. doi: 10.1016/j.mcn.2020.103494. Epub 2020 May 6.
Long interspersed nuclear elements-1 (LINE-1) are mobile DNA elements that comprise the majority of interspersed repeats in the mammalian genome. During the last decade, these transposable sequences have been described as controlling elements involved in transcriptional regulation and genome plasticity. Recently, LINE-1 have been implicated in neurogenesis, but to date little is known about their nuclear organization in neurons. The olfactory epithelium is a site of continuous neurogenesis, and loci of olfactory receptor genes are enriched in LINE-1 copies. Olfactory neurons have a unique inverted nuclear architecture and constitutive heterochromatin forms a block in the center of the nuclei. Our DNA FISH images show that, even though LINE-1 copies are dispersed throughout the mice genome, they are clustered forming a cap around the central heterochromatin block and frequently occupy the same position as facultative heterochromatin in olfactory neurons nuclei. This specific LINE-1 organization could not be observed in other olfactory epithelium cell types. Analyses of H3K27me3 and H3K9me3 ChIP-seq data from olfactory epithelium revealed that LINE-1 copies located at OR gene loci show different enrichment for these heterochromatin marks. We also found that LINE-1 are transcribed in mouse olfactory epithelium. These results suggest that LINE-1 play a role in the olfactory neurons' nuclear architecture. SIGNIFICANCE STATEMENT: LINE-1 are mobile DNA elements and comprise almost 20% of mice and human genomes. These retrotransposons have been implicated in neurogenesis. We show for the first time that LINE-1 retrotransposons have a specific nuclear organization in olfactory neurons, forming aggregates concentric to the heterochromatin block and frequently occupying the same region as facultative heterochromatin. We found that LINE-1 at olfactory receptor gene loci are differently enriched for H3K9me3 and H3K27me3, but LINE-1 transcripts could be detected in the olfactory epithelium. We speculate that these retrotransposons play an active role in olfactory neurons' nuclear architecture.
长散在核元件 1（LINE-1）是一种移动 DNA 元件，构成了哺乳动物基因组中大多数散在重复序列的主要部分。在过去的十年中，这些转座序列被描述为参与转录调控和基因组可塑性的调控元件。最近，LINE-1 被认为与神经发生有关，但迄今为止，人们对其在神经元中的核组织知之甚少。嗅上皮是连续发生神经发生的部位，嗅觉受体基因的位点富含 LINE-1 拷贝。嗅觉神经元具有独特的反转核结构，组成型异染色质形成核中心的块。我们的 DNA FISH 图像显示，即使 LINE-1 拷贝在小鼠基因组中分散存在，它们也会聚集形成围绕中央异染色质块的帽子，并经常占据嗅觉神经元核中兼性异染色质的相同位置。这种特定的 LINE-1 组织不能在其他嗅上皮细胞类型中观察到。对嗅上皮 H3K27me3 和 H3K9me3 ChIP-seq 数据的分析表明，位于 OR 基因位点的 LINE-1 拷贝对这些异染色质标记的富集程度不同。我们还发现 LINE-1 在小鼠嗅上皮中被转录。这些结果表明 LINE-1 在嗅觉神经元的核结构中发挥作用。意义陈述：LINE-1 是移动 DNA 元件，占小鼠和人类基因组的近 20%。这些反转录转座子已被牵涉到神经发生中。我们首次表明，LINE-1 反转录转座子在嗅觉神经元中有特定的核组织，形成围绕异染色质块的同心聚集物，并且经常占据与兼性异染色质相同的区域。我们发现，嗅觉受体基因位点上的 LINE-1 对 H3K9me3 和 H3K27me3 的富集程度不同，但在嗅上皮中可以检测到 LINE-1 转录本。我们推测这些反转录转座子在嗅觉神经元的核结构中发挥积极作用。
