Max Planck Institute for Molecular Genetics, 14195, Berlin, Germany.
Free University Berlin, 14195, Berlin, Germany.
Nat Commun. 2018 Apr 24;9(1):1636. doi: 10.1038/s41467-018-04100-3.
Long ncRNAs are often enriched in the nucleus and at chromatin, but whether their dissociation from chromatin is important for their role in transcription regulation is unclear. Here, we group long ncRNAs using epigenetic marks, expression and strength of chromosomal interactions; we find that long ncRNAs transcribed from loci engaged in strong long-range chromosomal interactions are less abundant at chromatin, suggesting the release from chromatin as a crucial functional aspect of long ncRNAs in transcription regulation of their target genes. To gain mechanistic insight into this, we functionally validate the long ncRNA A-ROD, which enhances DKK1 transcription via its nascent spliced released form. Our data provide evidence that the regulatory interaction requires dissociation of A-ROD from chromatin, with target specificity ensured within the pre-established chromosomal proximity. We propose that the post-transcriptional release of a subset of long ncRNAs from the chromatin-associated template plays an important role in their function as transcription regulators.
长链非编码 RNA 通常富含于细胞核和染色质中，但它们与染色质的解离是否对其在转录调控中的作用很重要尚不清楚。在这里，我们根据表观遗传标记、表达和染色体相互作用的强度对长链非编码 RNA 进行分组；我们发现，由参与强远距离染色体相互作用的基因座转录的长链非编码 RNA 在染色质上的丰度较低，这表明从染色质上释放是非编码 RNA 在其靶基因转录调控中的一个关键功能方面。为了深入了解这一机制，我们对长链非编码 RNA A-ROD 进行了功能验证，该 RNA 通过其新生剪接释放形式增强 DKK1 的转录。我们的数据提供了证据表明，这种调节相互作用需要 A-ROD 从染色质上解离，而在预先建立的染色体接近性内确保了靶标特异性。我们提出，一组长链非编码 RNA 从染色质相关模板的转录后释放，在其作为转录调节剂的功能中发挥着重要作用。
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