The bacterial cell cycle regulator GcrA is a σ⁷⁰ cofactor that drives gene expression from a subset of methylated promoters
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Haakonsen-2015-The bacterial cell c.pdf
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Author(s) • •
Haakonsen, Diane L.
Yuan, Andy H.
Laub, Michael T.
Date Issued
November 2015
Journal
Genes & Development
Publisher
Cold Spring Harbor Laboratory Press
Citation
Haakonsen, Diane L.; Yuan, Andy H. and Laub, Michael T. “The bacterial cell cycle regulator GcrA is a σ⁷⁰ cofactor that drives gene expression from a subset of methylated promoters ” Genes & Development 29, 21 (November 2015): 2272–2286 © 2015 Haakonsen et al
Version
Final published version
Abstract
Cell cycle progression in most organisms requires tightly regulated programs of gene expression. The transcription factors involved typically stimulate gene expression by binding specific DNA sequences in promoters and recruiting RNA polymerase. Here, we found that the essential cell cycle regulator GcrA in Caulobacter crescentus activates the transcription of target genes in a fundamentally different manner. GcrA forms a stable complex with RNA polymerase and localizes to almost all active σ⁷⁰-dependent promoters in vivo but activates transcription primarily at promoters harboring certain DNA methylation sites. Whereas most transcription factors that contact σ⁷⁰ interact with domain 4, GcrA interfaces with domain 2, the region that binds the −10 element during strand separation. Using kinetic analyses and a reconstituted in vitro transcription assay, we demonstrated that GcrA can stabilize RNA polymerase binding and directly stimulate open complex formation to activate transcription. Guided by these studies, we identified a regulon of ∼200 genes, providing new insight into the essential functions of GcrA. Collectively, our work reveals a new mechanism for transcriptional regulation, and we discuss the potential benefits of activating transcription by promoting RNA polymerase isomerization rather than recruitment exclusively.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Howard Hughes Medical Institute
Massachusetts Institute of Technology. Microbiology Graduate Program
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Creative Commons Attribution-NonCommercial 4.0 International
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DOI of Published Version
https://doi.org/10.1101/gad.270660.115