Genomic Repeats Categorize Genes with Distinct Functions for Orchestrated Regulation
Genomic Repeats Categorize Genes with Distinct Functions for Orchestrated Regulation
复制标题
基因组重复对具有不同功能的基因进行分类，以进行精心策划的调控
DOI：
10.1016/j.celrep.2020.02.048
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发表时间：
2020-03-10
期刊：
影响因子：
8.8
通讯作者：
Shen, Xiaohua
中科院分区：
文献类型：
--
作者：
Lu, J. Yuyang;Shao, Wen;Shen, Xiaohua
重复元件在哺乳动物基因组中广泛分布。在这里，我们揭示了一个惊人的重复亚型和基因功能之间的关联。SINE、L1和低复杂性重复序列划分了基因的不同功能类别，并可能通过为不同的调控蛋白提供结合位点来决定基因表达的时间和水平。重要的是，成像和测序分析表明，L1重复序列隔离了大量在核仁和核纤层相关的无活性结构域中具有专门功能的基因，这些结构域缺失了SINE重复序列。此外，L1转录本在胚胎干细胞（ESC）中广泛结合其DNA。ESCs中L1 RNA的缺失导致富含L1的染色体片段从非活性结构域重新定位到核内部，并解除L1相关基因的抑制。这些结果表明L1 DNA和RNA在基因沉默中的作用，并提出了基因组重复序列在协调其宿主基因的功能，调节和表达中的一般主题。
Repetitive elements are abundantly distributed in mammalian genomes. Here, we reveal a striking association between repeat subtypes and gene function. SINE, L1, and low-complexity repeats demarcate distinct functional categories of genes and may dictate the time and level of gene expression by providing binding sites for different regulatory proteins. Importantly, imaging and sequencing analysis show that L1 repeats sequester a large set of genes with specialized functions in nucleolus- and lamina-associated inactive domains that are depleted of SINE repeats. In addition, L1 transcripts bind extensively to its DNA in embryonic stem cells (ESCs). Depletion of L1 RNA in ESCs leads to relocation of L1-enriched chromosomal segments from inactive domains to the nuclear interior and derepression of L1-associated genes. These results demonstrate a role of L1 DNA and RNA in gene silencing and suggest a general theme of genomic repeats in orchestrating the function, regulation, and expression of their host genes.