Mammalian Genes Are Transcribed with Widely Different Bursting Kinetics
Mammalian Genes Are Transcribed with Widely Different Bursting Kinetics
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DOI：
10.1126/science.1198817
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发表时间：
2011-04-22
期刊：
影响因子：
56.9
通讯作者：
Naef, Felix
中科院分区：
文献类型：
--
作者：
Suter, David M.;Molina, Nacho;Naef, Felix
在原核生物和真核生物中，大多数基因似乎是在被称为转录爆发的短时间内转录的，其间穿插着沉默的间隔。我们描述了这种爆发如何在哺乳动物细胞中产生信使RNA（mRNA）合成的基因特异性时间模式。为了以高时间分辨率监测转录，我们建立了各种基因陷阱细胞系和转基因细胞系，这些细胞系从不稳定的mRNA表达短寿命的荧光素酶蛋白，并在单细胞中记录真实的时间生物发光。数学建模确定了基因特异性的转录活性的开关速率和在爆发期间产生的mRNA的平均数量。转录动力学显着改变顺式调控DNA元件。我们的分析表明，爆发动力学是高度基因特异性的，反映了不应期，在此期间，基因在再次开启之前保持一定时间的不活动。
In prokaryotes and eukaryotes, most genes appear to be transcribed during short periods called transcriptional bursts, interspersed by silent intervals. We describe how such bursts generate gene-specific temporal patterns of messenger RNA (mRNA) synthesis in mammalian cells. To monitor transcription at high temporal resolution, we established various gene trap cell lines and transgenic cell lines expressing a short-lived luciferase protein from an unstable mRNA, and recorded bioluminescence in real time in single cells. Mathematical modeling identified gene-specific on-and off-switching rates in transcriptional activity and mean numbers of mRNAs produced during the bursts. Transcriptional kinetics were markedly altered by cis-regulatory DNA elements. Our analysis demonstrated that bursting kinetics are highly gene-specific, reflecting refractory periods during which genes stay inactive for a certain time before switching on again.