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The Influence of Repressor DNA Binding Site Architecture on Transcriptional Control

Journal Article · · mBio (Online)
 [1];  [2]
  1. Univ. of Wisconsin, Madison, WI (United States). Dept. of Biomolecular Chemistry; DOE/OSTI
  2. Univ. of Wisconsin, Madison, WI (United States). Dept. of Biomolecular Chemistry

How the architecture of DNA binding sites dictates the extent of repression of promoters is not well understood. Here, we addressed the importance of the number and information content of the three direct repeats (DRs) in the binding and repression of the icdA promoter by the phosphorylated form of the global Escherichia coli repressor ArcA (ArcA-P). We show that decreasing the information content of the two sites with the highest information (DR1 and DR2) eliminated ArcA binding to all three DRs and ArcA repression of icdA. Unexpectedly, we also found that DR3 occupancy functions principally in repression, since mutation of this low-information-content site both eliminated DNA binding to DR3 and significantly weakened icdA repression, despite the fact that binding to DR1 and DR2 was intact. In addition, increasing the information content of any one of the three DRs or addition of a fourth DR increased ArcA-dependent repression but perturbed signal-dependent regulation of repression. Thus, our data show that the information content and number of DR elements are critical architectural features for maintaining a balance between high-affinity binding and signal-dependent regulation of icdA promoter function in response to changes in ArcA-P levels. Optimization of such architectural features may be a common strategy to either dampen or enhance the sensitivity of DNA binding among the members of the large OmpR/PhoB family of regulators as well as other transcription factors.

Research Organization:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
FG02-04ER25627
OSTI ID:
1626136
Journal Information:
mBio (Online), Journal Name: mBio (Online) Journal Issue: 5 Vol. 5; ISSN 2150-7511
Publisher:
American Society for Microbiology (ASM)Copyright Statement
Country of Publication:
United States
Language:
English

References (49)

Inhibition of Transcription Initiation buIacRepressor journal January 1995
DNA Binding of PhoB and its Interaction with RNA Polymerase journal May 1996
Information Content of Individual Genetic Sequences journal December 1997
A mutational study of the ArcA-P binding sequences in the aldA promoter of Escherichia coli journal February 1999
Sequence-Specific Binding to a Subset of IscR-Regulated Promoters Does Not Require IscR Fe–S Cluster Ligation journal March 2009
Probing the Roles of the Two Different Dimers Mediated by the Receiver Domain of the Response Regulator PhoB journal June 2009
Comprehensive Analysis of OmpR Phosphorylation, Dimerization, and DNA Binding Supports a Canonical Model for Activation journal May 2013
Bacterial response regulators: versatile regulatory strategies from common domains journal May 2007
An asymmetric heterodomain interface stabilizes a response regulator–DNA complex journal February 2014
Design of stable and self-regulated microbial consortia for chemical synthesis journal March 2022
A search for amino acid substitutions that universally activate response regulators: Activating substitutions in response regulators journal December 2003
Identification of a quinone-sensitive redox switch in the ArcB sensor kinase journal August 2004
Promoters largely determine the efficiency of repressor action. journal December 1988
Cross-induction of glc and ace Operons of Escherichia coli Attributable to Pathway Intersection : CHARACTERIZATION OF THE journal January 1999
Multimerization of Phosphorylated and Non-phosphorylated ArcA Is Necessary for the Response Regulator Function of the Arc Two-component Signal Transduction System journal November 2001
Transcript Profiling and Inference of Escherichia coli K-12 ArcA Activity across the Range of Physiologically Relevant Oxygen Concentrations journal March 2011
Probing the ArcA-P Modulon of Escherichia coli by Whole Genome Transcriptional Analysis and Sequence Recognition Profiling journal March 2004
Signaling by the Arc Two-Component System Provides a Link Between the Redox State of the Quinone Pool and Gene Expression journal May 2006
Sequence walkers: A graphical method to display how binding proteins interact with DNA or RNA sequences journal November 1997
Discovery of Fur binding site clusters in Escherichia coli by information theory models journal October 2007
A high-throughput percentage-of-binding strategy to measure binding energies in DNA–protein interactions: application to genome-scale site discovery journal July 2008
EcoCyc: a comprehensive database of Escherichia coli biology journal November 2010
Position and density effects on repression by stationary and mobile DNA-binding proteins. journal February 1989
Co-regulation of lipoamide dehydrogenase and 2-oxoglutarate dehydrogenase synthesis in Escherichia coli : characterisation of an ArcA binding site in the lpd promoter journal December 1998
Transcriptional control mediated by the ArcA two-component response regulator protein of Escherichia coli: characterization of DNA binding at target promoters. journal January 1996
Cra-Dependent Transcriptional Activation of theicd Gene of Escherichia coli journal February 1999
Genome-Wide Expression Analysis Indicates that FNR of Escherichia coli K-12 Regulates a Large Number of Genes of Unknown Function journal January 2005
The Bacterial Response Regulator ArcA Uses a Diverse Binding Site Architecture to Regulate Carbon Oxidation Globally journal October 2013
The bacterial LexA transcriptional repressor journal August 2008
DNA structural variations in the E. coli tyrT promoter journal June 1984
The OmpR protein of Escherichia coli binds to sites in the ompF promoter region in a hierarchical manner determined by its degree of phosphorylation. journal April 1994
Free energy coupling within macromolecules journal October 1983
[57] Sequencing end-labeled DNA with base-specific chemical cleavages book January 1980
Tandem DNA Recognition by PhoB, a Two-Component Signal Transduction Transcriptional Activator journal May 2002
Structural Analysis and Solution Studies of the Activated Regulatory Domain of the Response Regulator ArcA: A Symmetric Dimer Mediated by the α4-β5-α5 Face journal May 2005
Cooperative Binding of PhoB DBD to Its Cognate DNA Sequence—A Combined Application of Single-Molecule and Ensemble Methods journal November 2013
Programming gene expression with combinatorial promoters journal January 2007
A weight matrix for binding recognition by the redox-response regulator ArcA-P of Escherichia coli journal April 1999
One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products journal May 2000
Multimerization of Phosphorylated and Non-phosphorylated ArcA Is Necessary for the Response Regulator Function of the Arc Two-component Signal Transduction System journal November 2001
Transcript Profiling and Inference of Escherichia coli K-12 ArcA Activity across the Range of Physiologically Relevant Oxygen Concentrations journal March 2011
Probing the ArcA-P Modulon of Escherichia coli by Whole Genome Transcriptional Analysis and Sequence Recognition Profiling journal March 2004
Transcription Regulation of ompF and ompC by a Single Transcription Factor, OmpR journal April 2006
Purification of ArcA and analysis of is specific interaction with the pfl promoter-regulatory region journal May 1995
Culture Medium for Enterobacteria journal January 1974
Cra-Dependent Transcriptional Activation of theicd Gene of Escherichia coli journal February 1999
Genome-Wide Expression Analysis Indicates that FNR of Escherichia coli K-12 Regulates a Large Number of Genes of Unknown Function journal January 2005
Culture Medium for Enterobacteria journal January 1974
Aerobic regulation of isocitrate dehydrogenase gene (icd) expression in Escherichia coli by the arcA and fnr gene products. journal January 1997

Cited By (9)

The MerR-like protein BldC binds DNA direct repeats as cooperative multimers to regulate Streptomyces development journal March 2018
Structure-function analysis of the DNA-binding domain of a transmembrane transcriptional activator journal April 2017
The coordinated action of RNase III and RNase G controls enolase expression in response to oxygen availability in Escherichia coli journal November 2019
Temporal Hierarchy of Gene Expression Mediated by Transcription Factor Binding Affinity and Activation Dynamics journal July 2015
Parametric bootstrapping for biological sequence motifs journal October 2016
Plasticity in oligomerization, operator architecture, and DNA binding in the mode of action of a bacterial B 12 -based photoreceptor journal September 2018
Transcriptomics analysis defines global cellular response of Agrobacterium tumefaciens 5A to arsenite exposure regulated through the histidine kinases PhoR and AioS journal April 2019
The Phosphohistidine Phosphatase SixA Targets a Phosphotransferase System journal November 2018
Coordinated regulation of acid resistance in Escherichia coli journal January 2017

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