Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.
Commun Biol. 2020 Feb 11;3(1):60. doi: 10.1038/s42003-020-0784-9.
In the nucleus, genomic DNA is wrapped around histone octamers to form nucleosomes. In principle, nucleosomes are substantial barriers to transcriptional activities. Nuclear non-coding RNAs (ncRNAs) are proposed to function in chromatin conformation modulation and transcriptional regulation. However, it remains unclear how ncRNAs affect the nucleosome structure. Eleanors are clusters of ncRNAs that accumulate around the estrogen receptor-α (ESR1) gene locus in long-term estrogen deprivation (LTED) breast cancer cells, and markedly enhance the transcription of the ESR1 gene. Here we detected nucleosome depletion around the transcription site of Eleanor2, the most highly expressed Eleanor in the LTED cells. We found that the purified Eleanor2 RNA fragment drastically destabilized the nucleosome in vitro. This activity was also exerted by other ncRNAs, but not by poly(U) RNA or DNA. The RNA-mediated nucleosome destabilization may be a common feature among natural nuclear RNAs, and may function in transcription regulation in chromatin.
在核内，基因组 DNA 缠绕在组蛋白八聚体周围形成核小体。原则上，核小体是转录活性的主要障碍。核非编码 RNA（ncRNA）被认为在染色质构象调节和转录调控中发挥作用。然而，ncRNA 如何影响核小体结构仍不清楚。Eleanors 是一组 ncRNA，它们在长期雌激素剥夺（LTED）乳腺癌细胞中聚集在雌激素受体-α（ESR1）基因座周围，显著增强 ESR1 基因的转录。在这里，我们检测到 Eleanor2 转录起始位点周围的核小体耗竭，Eleanor2 是 LTED 细胞中表达量最高的 Eleanor。我们发现纯化的 Eleanor2 RNA 片段在体外剧烈破坏核小体。其他 ncRNA 也具有这种活性，但 poly(U) RNA 或 DNA 没有这种活性。这种 RNA 介导的核小体去稳定化可能是天然核 RNA 的共同特征，并可能在染色质转录调控中发挥作用。
