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DOI10.1073/PNAS.2020204117
Rewiring the specificity of extracytoplasmic function sigma factors
Todor H.; Osadnik H.; Campbell E.A.; Myers K.S.; Li H.; Donohue T.J.; Gross C.A.
发表日期2021
ISSN00278424
起始页码33496
结束页码33506
卷号117期号:52
英文摘要Bacterial genomes are being sequenced at an exponentially increasing rate, but our inability to decipher their transcriptional wiring limits our ability to derive new biology from these sequences. De novo determination of regulatory interactions requires accurate prediction of regulators’ DNA binding and precise determination of biologically significant binding sites. Here we address these challenges by solving the DNA-specificity code of extracytoplasmic function sigma factors (ECF σs), a major family of bacterial regulators, and determining their putative regulons. We generated an aligned collection of ECF σs and their promoters by leveraging the autoregulatory nature of ECF σs as a means of promoter discovery and analyzed it to identify and characterize the conserved amino acid–nucleotide interactions that determine promoter specificity. This enabled de novo prediction of ECF σ specificity, which we combined with a statistically rigorous phylogenetic footprinting pipeline based on precomputed orthologs to predict the direct targets of ∼67% of ECF σs. This global survey indicated that some ECF σs are conserved global regulators controlling many genes throughout the genome, which are important under many conditions, while others are local regulators, controlling a few closely linked genes in response to specific stimuli in select species. This analysis reveals important organizing principles of bacterial gene regulation and presents a conceptual and computational framework for deciphering gene regulatory networks. © 2020 National Academy of Sciences. All rights reserved.
英文关键词Bioinformatics; Phylogenetic footprinting; Sigma factors; Transcriptional regulation
语种英语
scopus关键词bacterial DNA; protein binding; sigma factor; cytoplasm; gene expression regulation; genetics; metabolism; molecular model; mutation; phylogeny; promoter region; regulon; Cytoplasm; DNA, Bacterial; Gene Expression Regulation, Bacterial; Models, Molecular; Mutation; Phylogeny; Promoter Regions, Genetic; Protein Binding; Regulon; Sigma Factor
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/179630
作者单位Department of Microbiology and Immunology, University of California, San Francisco, CA 94158, United States; Laboratory of Molecular Biophysics, Rockefeller University, New York, NY 10065, United States; Wisconsin Energy Institute, University of Wisconsin–Madison, Madison, WI 53726, United States; Great Lakes Bioenergy Research Center, University of Wisconsin–Madison, Madison, WI 53726, United States; California Institute of Quantitative Biology, University of California, San Francisco, CA 94158, United States; Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, United States; Department of Bacteriology, University of Wisconsin–Madison, Madison, WI 53706, United States; Department of Cell and Tissue Biology, University of California, San Francisco, CA 94158, United States
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Todor H.,Osadnik H.,Campbell E.A.,et al. Rewiring the specificity of extracytoplasmic function sigma factors[J],2021,117(52).
APA Todor H..,Osadnik H..,Campbell E.A..,Myers K.S..,Li H..,...&Gross C.A..(2021).Rewiring the specificity of extracytoplasmic function sigma factors.Proceedings of the National Academy of Sciences of the United States of America,117(52).
MLA Todor H.,et al."Rewiring the specificity of extracytoplasmic function sigma factors".Proceedings of the National Academy of Sciences of the United States of America 117.52(2021).
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