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Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation

机译：增强RNA在雌激素依赖性转录激活中的功能作用

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摘要

The functional importance of gene enhancers in regulated gene expression is well established. In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation. Here we report that in human breast cancer cells 17β-oestradiol (E2)-bound oestrogen receptor a (ER-α) causes a global increase in eRNA transcription on enhancers adjacent to E2-upregulated coding genes. These induced eRNAs, as functional transcripts, seem to exert important roles for the observed ligand-dependent induction of target coding genes, increasing the strength of specific enhancer-promoter looping initiated by ER-α binding. Cohesin, present on many ER-α-regulated enhancers even before ligand treatment, apparently contributes to E2-dependent gene activation, at least in part by stabilizing E2/ER-α/eRNA-induced enhancer-promoter looping. Our data indicate that eRNAs are likely to have important functions in many regulated programs of gene transcription.
机译：众所周知，基因增强子在调控基因表达中的功能重要性。除了在哺乳动物细胞中长的非编码RNA（lncRNA）的广泛转录外，双向ncRNA也转录在增强子上，因此被称为增强子RNA（eRNA）。然而，还不清楚这些eRNA是功能性的还是仅仅是增强子激活的反映。在这里，我们报道在人类乳腺癌细胞中17β-雌二醇（E2）结合的雌激素受体a（ER-α）导致与E2上调的编码基因相邻的增强子上eRNA转录的整体增加。这些诱导的eRNA，作为功能性转录物，似乎在观察到的目标编码基因的配体依赖性诱导中发挥重要作用，从而增加了由ER-α结合引发的特定增强子-启动子环的强度。甚至在配体处理之前，许多ER-α调节的增强子上都存在的粘着素显然有助于E2依赖的基因激活，至少部分是通过稳定E2 /ER-α/ eRNA诱导的增强子-启动子环。我们的数据表明，eRNA在许多受调控的基因转录程序中可能具有重要功能。

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  • 来源
    《Nature》 |2013年第7455期|516-520|共5页
  • 作者

    Wenbo Li; Dimple Notani; Qi Ma; Bogdan Tanasa; Esperanza Nunez; Aaron Yun Chen; Daria Merkurjev; Jie Zhang; Kenneth Ohgi; Xiaoyuan Song; Soohwan Oh; Hong-Sook Kim; Christopher K. Glass; Michael G. Rosenfeld;

  • 作者单位

    Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.;

    Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.;

    Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA, Graduate Program in Bioinformatics, University of California, San Diego, La Jolla, California 92093, USA.;

    Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA, Graduate Program, Kellogg School of Science and Technology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.;

    Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.;

    Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.;

    Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA, Graduate Program in Bioinformatics, University of California, San Diego, La Jolla, California 92093, USA.;

    Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.;

    Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.;

    Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.;

    Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA, Graduate Program in Biological Sciences, University of California, San Diego, La Jolla, California 92093, USA.;

    Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.;

    Cellular and Molecular Medicine, Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA;

    Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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