Rewiring the specificity of extracytoplasmic function sigma factors.
bioinformatics
phylogenetic footprinting
sigma factors
transcriptional regulation
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
29 12 2020
29 12 2020
Historique:
pubmed:
16
12
2020
medline:
11
2
2021
entrez:
15
12
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33318184
pii: 2020204117
doi: 10.1073/pnas.2020204117
pmc: PMC7776599
doi:
Substances chimiques
DNA, Bacterial
0
Sigma Factor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
33496-33506Subventions
Organisme : NIA NIH HHS
ID : R01 AG058742
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM114450
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118061
Pays : United States
Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Competing interest statement: T.J.D., C.A.G., and M.J.B. are coauthors on a 2019 review article. C.A.G. and M.J.B. are coauthors on a consortium paper [D. Casas-Pastor et al., bioRxiv:2019.12.11.873521 (2019)].
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