Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA.
Genes Dev. 2011 Jul 15;25(14):1486-98. doi: 10.1101/gad.2059211.
Transcriptional regulation of developmentally controlled genes is at the heart of differentiation and organogenesis. In this study, we performed global genomic analyses in murine embryonic stem (ES) cells and in human cells in response to activation signals. We identified an essential role for the ELL (eleven-nineteen lysine-rich leukemia gene)/P-TEFb (positive transcription elongation factor)-containing super elongation complex (SEC) in the regulation of gene expression, including several genes bearing paused RNA polymerase II (Pol II). Paused Pol II has been proposed to be associated with loci that respond rapidly to environmental stimuli. However, our studies in ES cells also identified a requirement for SEC at genes without paused Pol II, which also respond dynamically to differentiation signals. Our findings suggest that SEC is a major class of active P-TEFb-containing complexes required for transcriptional activation in response to environmental cues such as differentiation signals.
发育控制基因的转录调控是分化和器官发生的核心。在这项研究中，我们在响应激活信号的小鼠胚胎干细胞和人类细胞中进行了全基因组分析。我们确定了 ELL（eleven-nineteen lysine-rich leukemia gene）/P-TEFb（positive transcription elongation factor）包含的超级延伸复合物（SEC）在基因表达调控中的重要作用，包括几个具有暂停 RNA 聚合酶 II（Pol II）的基因。暂停的 Pol II 被认为与快速响应环境刺激的基因座有关。然而，我们在 ES 细胞中的研究还发现，SEC 在没有暂停 Pol II 的基因中也有需求，这些基因也对分化信号做出动态响应。我们的研究结果表明，SEC 是一类主要的含有 P-TEFb 的活性复合物，在响应环境信号（如分化信号）时，对转录激活是必需的。
