Bursty gene expression in the intact mammalian liver.
Bursty gene expression in the intact mammalian liver.
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完整的哺乳动物肝中的爆发基因表达。
DOI：
10.1016/j.molcel.2015.01.027
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发表时间：
2015-04-02
期刊：
影响因子：
16
通讯作者：
Itzkovitz S
中科院分区：
文献类型：
--
作者：
Bahar Halpern K;Tanami S;Landen S;Chapal M;Szlak L;Hutzler A;Nizhberg A;Itzkovitz S
新生mRNA的爆发已被证明会导致单细胞生物中大量的细胞间变异，促进对环境挑战的多样化反应。目前还不清楚在哺乳动物组织中是否会发生类似的爆发和基因表达噪音。为了解决这个问题，我们结合联合收割机单分子转录计数与双色标记和定量的新生mRNA的启动子状态，转录速率和转录寿命在完整的小鼠肝脏的特点。我们发现肝脏基因表达是高度突发的，启动子在转录活性和非活性状态之间随机切换。mRNA寿命短的基因的启动子活性更长，促进快速反应，同时减少与突发相关的噪音。此外，多倍体肝细胞比二倍体肝细胞表现出更少的噪音，这表明可能有利于肝脏多倍体。因此，时间平均和肝脏多倍体抑制与转录爆发相关的内在变异性。我们的方法可用于研究不同哺乳动物组织中的转录爆发。
Bursts of nascent mRNA have been shown to lead to substantial cell-cell variation in unicellular organisms, facilitating diverse responses to environmental challenges. It is unknown whether similar bursts and gene-expression noise occur in mammalian tissues. To address this, we combine single molecule transcript counting with dual-color labeling and quantification of nascent mRNA to characterize promoter states, transcription rates and transcript lifetimes in the intact mouse liver. We find that liver gene expression is highly bursty, with promoters stochastically switching between transcriptionally active and inactive states. Promoters of genes with short mRNA lifetimes are active longer, facilitating rapid response while reducing burst-associated noise. Moreover, polyploid hepatocytes exhibit less noise than diploid hepatocytes, suggesting a possible benefit to liver polyploidy. Thus temporal averaging and liver polyploidy dampen the intrinsic variability associated with transcriptional bursts. Our approach can be used to study transcriptional bursting in diverse mammalian tissues.