Population-Level Transcription Cycles Derive from Stochastic Timing of Single-Cell Transcription (Retracted article. See vol. 143, pg. 651, 2010)
Population-Level Transcription Cycles Derive from Stochastic Timing of Single-Cell Transcription (Retracted article. See vol. 143, pg. 651, 2010)
复制标题
DOI：
10.1016/j.cell.2009.05.029
复制
发表时间：
2009-08-07
期刊：
影响因子：
64.5
通讯作者：
Carlberg, Carsten
中科院分区：
文献类型：
--
作者：
Degenhardt, Tatjana;Rybakova, Katja N.;Carlberg, Carsten
真核转录是一个依赖于大量蛋白质的动态过程。通过测量丙酮酸脱氢酶激酶4基因在人类细胞中的循环表达，我们构建了一个详细的随机模型，在分子水平上的单基因转录扩散和蛋白质复合物动力学的现实动力学。我们观察到，基因诱导引起了大约60分钟的周期性的几个转录相关的过程：第一，共价组蛋白修饰和存在的许多调节蛋白在转录起始位点;第二，RNA聚合酶II的活性;第三，染色质环的形成;和第四，mRNA的积累。当我们考虑到转录起始的顺序和不可逆的多步性质时，我们的模型可以预测单基因活性导致细胞群体水平上的转录循环的精确时间。我们提出，群体基因表达的周期性主要是基于转录过程本身的内在周期性。
Eukaryotic transcription is a dynamic process relying on a large number of proteins. By measuring the cycling expression of the pyruvate dehydrogenase kinase 4 gene in human cells, we constructed a detailed stochastic model for single-gene transcription at the molecular level using realistic kinetics for diffusion and protein complex dynamics. We observed that gene induction caused an approximate 60 min periodicity of several transcription related processes: first, the covalent histone modifications and presence of many regulatory proteins at the transcription start site; second, RNA polymerase II activity; third, chromatin loop formation; and fourth, mRNA accumulation. Our model can predict the precise timing of single-gene activity leading to transcriptional cycling on the cell population level when we take into account the sequential and irreversible multistep nature of transcriptional initiation. We propose that the cyclic nature of population gene expression is primarily based on the intrinsic periodicity of the transcription process itself.