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Genomic encoding of transcriptional burst kinetics

机译：转录爆发动力学的基因组编码

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摘要

Mammalian gene expression is inherently stochastic(1,2), and results in discrete bursts of RNA molecules that are synthesized from each allele(3-7). Although transcription is known to be regulated by promoters and enhancers, it is unclear how cis-regulatory sequences encode transcriptional burst kinetics. Characterization of transcriptional bursting, including the burst size and frequency, has mainly relied on live-cell(4,6,8) or single-molecule RNA fluorescence in situ hybridization(3,5,8,9) recordings of selected loci. Here we determine transcriptome-wide burst frequencies and sizes for endogenous mouse and human genes using allele-sensitive single-cell RNA sequencing. We show that core promoter elements affect burst size and uncover synergistic effects between TATA and initiator elements, which were masked at mean expression levels. Notably, we provide transcriptome-wide evidence that enhancers control burst frequencies, and demonstrate that cell-type-specific gene expression is primarily shaped by changes in burst frequencies. Together, our data show that burst frequency is primarily encoded in enhancers and burst size in core promoters, and that allelic single-cell RNA sequencing is a powerful model for investigating transcriptional kinetics.
机译：哺乳动物基因表达固有地是随机的（1,2），并导致从每个等位基因合成的RNA分子离散爆发（3-7）。尽管已知转录受启动子和增强子调控，但尚不清楚顺式调控序列如何编码转录爆发动力学。转录爆发的特征，包括爆发的大小和频率，主要取决于所选位点的活细胞（4,6,8）或单分子RNA荧光原位杂交（3,5,8,9）记录。在这里，我们使用等位基因敏感的单细胞RNA测序确定内源性小鼠和人类基因的转录组范围内的爆发频率和大小。我们显示核心启动子元素影响突发大小，并发现TATA和启动子元素之间的协同效应，这些效应被平均表达水平所掩盖。值得注意的是，我们提供了转录组范围内增强子控制猝发频率的证据，并证明细胞类型特异性基因表达主要受猝发频率变化的影响。总之，我们的数据表明，猝发频率主要编码在核心启动子的增强子和猝发大小中，等位基因单细胞RNA测序是研究转录动力学的强大模型。

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  • 来源
    《Nature》 |2019年第7738期|251-254|共4页
  • 作者

    Larsson Anton J. M.; Johnsson Per; Hagemann-Jensen Michael; Hartmanis Leonard; Faridani Omid R.; Reinius Bjorn; Segerstolpe Asa; Rivera Chloe M.; Ren Bing; Sandberg Rickard;

  • 作者单位

    Karolinska Inst Dept Cell & Mol Biol Stockholm Sweden;

    Karolinska Inst Dept Cell & Mol Biol Stockholm Sweden|Ludwig Inst Canc Res Stockholm Sweden;

    Karolinska Inst Dept Cell & Mol Biol Stockholm Sweden|Karolinska Inst Integrated Cardio Metab Ctr ICMC Stockholm Sweden;

    Karolinska Inst Dept Cell & Mol Biol Stockholm Sweden|Ludwig Inst Canc Res Stockholm Sweden|Karolinska Inst Dept Med Biochem & Biophys Stockholm Sweden;

    Karolinska Inst Dept Cell & Mol Biol Stockholm Sweden|Karolinska Inst Integrated Cardio Metab Ctr ICMC Stockholm Sweden|Broad Inst MIT & Harvard Klarman Cell Observ Cambridge MA USA;

    Ludwig Inst Canc Res San Diego CA USA|Univ Calif San Diego Sch Med Dept Cellular & Mol Med La Jolla CA 92093 USA;

    Karolinska Inst Dept Cell & Mol Biol Stockholm Sweden|Ludwig Inst Canc Res Stockholm Sweden|Karolinska Inst Integrated Cardio Metab Ctr ICMC Stockholm Sweden;

  • 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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