Facciotti Marc T, Reiss David J, Pan Min, Kaur Amardeep, Vuthoori Madhavi, Bonneau Richard, Shannon Paul, Srivastava Alok, Donohoe Samuel M, Hood Leroy E, Baliga Nitin S
Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98121, USA.
Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4630-5. doi: 10.1073/pnas.0611663104. Epub 2007 Mar 7.
Cells responding to dramatic environmental changes or undergoing a developmental switch typically change the expression of numerous genes. In bacteria, sigma factors regulate much of this process, whereas in eukaryotes, four RNA polymerases and a multiplicity of generalized transcription factors (GTFs) are required. Here, by using a systems approach, we provide experimental evidence (including protein-coimmunoprecipitation, ChIP-Chip, GTF perturbation and knockout, and measurement of transcriptional changes in these genetically perturbed strains) for how archaea likely accomplish similar large-scale transcriptional segregation and modulation of physiological functions. We are able to associate GTFs to nearly half of all putative promoters and show evidence for at least 7 of the possible 42 functional GTF pairs. This report represents a significant contribution toward closing the gap in our understanding of gene regulation by GTFs for all three domains of life and provides an example for how to use various experimental techniques to rapidly learn significant portions of a global gene regulatory network of organisms for which little has been previously known.
对剧烈环境变化作出反应或经历发育转变的细胞通常会改变众多基因的表达。在细菌中,σ因子调控这一过程的大部分,而在真核生物中,则需要四种RNA聚合酶和多种通用转录因子(GTF)。在这里,我们通过系统方法,提供了实验证据(包括蛋白质共免疫沉淀、芯片杂交、GTF干扰和敲除,以及对这些基因扰动菌株中转录变化的测量),以说明古细菌可能如何完成类似的大规模转录分离和生理功能调节。我们能够将GTF与几乎所有推定启动子的近一半关联起来,并为42种可能的功能性GTF对中的至少7种提供了证据。本报告为缩小我们对生命所有三个域中GTF基因调控理解上的差距做出了重大贡献,并提供了一个示例,说明如何使用各种实验技术快速了解此前知之甚少的生物体全局基因调控网络的重要部分。