DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: TroR is the primary regulator of the iron homeostasis transcription network in the halophilic archaeon Haloferax volcanii

Journal Article · · Nucleic Acids Research

Maintaining the intracellular iron concentration within the homeostatic range is vital to meet cellular metabolic needs and reduce oxidative stress. Previous research revealed that the haloarchaeon Halobacterium salinarum encodes four diphtheria toxin repressor (DtxR) family transcription factors (TFs) that together regulate the iron response through an interconnected transcriptional regulatory network (TRN). However, the conservation of the TRN and the metal specificity of DtxR TFs remained poorly understood. Here we identified and characterized the TRN of Haloferax volcanii for comparison. Genetic analysis demonstrated that Hfx. volcanii relies on three DtxR transcriptional regulators (Idr, SirR, and TroR), with TroR as the primary regulator of iron homeostasis. Bioinformatics and molecular approaches revealed that TroR binds a conserved cis-regulatory motif located ~100 nt upstream of the start codon of iron-related target genes. Transcriptomics analysis demonstrated that, under conditions of iron sufficiency, TroR repressed iron uptake and induced iron storage mechanisms. TroR repressed the expression of one other DtxR TF, Idr. This reduced DtxR TRN complexity relative to that of Hbt. salinarum appeared correlated with natural variations in iron availability. Based on these data, we hypothesize that variable environmental conditions such as iron availability appear to select for increasing TRN complexity.

Research Organization:
Univ. of Florida, Gainesville, FL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division (CSGB); National Science Foundation (NSF); National Institutes of Health (NIH); USDOE
Grant/Contract Number:
FG02-05ER15650; MCB 1651117; 1936024; NIH R01 GM057498; DOE DE-FG02-05ER15650
OSTI ID:
2217632
Alternate ID(s):
OSTI ID: 2472248
Journal Information:
Nucleic Acids Research, Vol. 52, Issue 1; ISSN 0305-1048
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English

References (70)

An archaeal histone-like protein regulates gene expression in response to salt stress journal December 2021
SnapShot: Network Motifs journal October 2010
Iron/sulfur proteins biogenesis in prokaryotes: Formation, regulation and diversity journal March 2013
Operon-mapper: a web server for precise operon identification in bacterial and archaeal genomes journal June 2018
Iron homeostasis and oxidative stress: An intimate relationship journal December 2019
Gene regulatory networks and the role of robustness and stochasticity in the control of gene expression journal February 2011
Sequence and expression of a halobacterial beta-galactosidase gene journal April 2000
Temporal variation of planetary iron as a driver of evolution journal December 2021
Updated clusters of orthologous genes for Archaea: a complex ancestor of the Archaea and the byways of horizontal gene transfer journal January 2012
igv.js: an embeddable JavaScript implementation of the Integrative Genomics Viewer (IGV) journal December 2022
Metal homeostasis and resistance in bacteria journal March 2017
Comparative Analysis of rRNA Removal Methods for RNA-Seq Differential Expression in Halophilic Archaea journal May 2022
Polyploidy in haloarchaea: advantages for growth and survival journal June 2014
MtsABC Is Important for Manganese and Iron Transport, Oxidative Stress Resistance, and Virulence of Streptococcus pyogenes journal May 2003
Phylogenetic analyses of some extremely halophilic archaea isolated from Dead Sea water, determined on the basis of their 16S rRNA sequences journal October 1996
Regulatory Activities of Four ArsR Proteins in Agrobacterium tumefaciens 5A journal June 2016
A workflow for genome-wide mapping of archaeal transcription factors with ChIP-seq journal February 2012
The Ribbon-Helix-Helix Domain Protein CdrS Regulates the Tubulin Homolog ftsZ2 To Control Cell Division in Archaea journal August 2020
Chromatin immunoprecipitation (ChIP) coupled to detection by quantitative real-time PCR to study transcription factor binding to DNA in Caenorhabditis elegans journal April 2008
Regulated Iron Siderophore Production of the Halophilic Archaeon Haloferax volcanii journal July 2020
Bacterial iron homeostasis journal June 2003
Extreme zinc tolerance in acidophilic microorganisms from the bacterial and archaeal domains journal November 2012
Iron-uptake in the Euryarchaeon Halobacterium salinarum journal January 2007
Direct multiplexed measurement of gene expression with color-coded probe pairs journal February 2008
Growthcurver: an R package for obtaining interpretable metrics from microbial growth curves journal April 2016
Nitrogen regulation of protein-protein interactions and transcript levels of GlnK PII regulator and AmtB ammonium transporter homologs in Archaea journal August 2013
Genomic analysis reveals a tight link between transcription factor dynamics and regulatory network architecture journal January 2009
The MEME Suite journal May 2015
A system‐level model for the microbial regulatory genome journal July 2014
Cell division in the archaeon Haloferax volcanii relies on two FtsZ proteins with distinct functions in division ring assembly and constriction journal April 2021
The Complete Genome Sequence of Haloferax volcanii DS2, a Model Archaeon journal March 2010
Iron and metal regulation in bacteria journal April 2001
A Predictive Model for Transcriptional Control of Physiology in a Free Living Cell journal December 2007
Development of a Gene Knockout System for the Halophilic Archaeon Haloferax volcanii by Use of the pyrE Gene journal February 2003
Two transcription factors are necessary for iron homeostasis in a salt-dwelling archaeon journal November 2010
Archaeal Genomics: An Overview journal June 1997
The gene for a halophilic beta-galactosidase (bgaH) of Haloferax alicantei as a reporter gene for promoter analyses in Halobacterium salinarum journal April 2000
Structure of the metal-ion-activated diphtheria toxin repressor/ tox operator complex journal July 1998
MntR(Rv2788): a transcriptional regulator that controls manganese homeostasis in M ycobacterium tuberculosis : Regulation of Mn homeostasis in Mtb journal October 2015
A transcription network of interlocking positive feedback loops maintains intracellular iron balance in archaea journal August 2017
AnnoTree: visualization and exploration of a functionally annotated microbial tree of life journal April 2019
Protein-DNA binding dynamics predict transcriptional response to nutrients in archaea journal July 2013
Iron-oxo clusters biomineralizing on protein surfaces: Structural analysis of Halobacterium salinarum DpsA in its low- and high-iron states journal September 2004
trackViewer: a Bioconductor package for interactive and integrative visualization of multi-omics data journal May 2019
Iron in the Dead Sea journal December 1984
Development of Additional Selectable Markers for the Halophilic Archaeon Haloferax volcanii Based on the leuB and trpA Genes journal February 2004
A role for the DtxR family of metalloregulators in gram-positive pathogenesis journal February 2014
Halobacterium volcanii spec. nov., a Dead Sea halobacterium with a moderate salt requirement journal January 1975
Evolution of a novel lysine decarboxylase in siderophore biosynthesis: A novel lysine decarboxylase journal August 2012
Iron Availability Influences the Tolerance of Southern Ocean Phytoplankton to Warming and Elevated Irradiance journal November 2019
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding journal May 1976
The human Golgi protein TMEM165 transports calcium and manganese in yeast and bacterial cells journal March 2020
Fast gapped-read alignment with Bowtie 2 journal March 2012
N-Glycosylation Is Important for Halobacterium salinarum Archaellin Expression, Archaellum Assembly and Cell Motility journal June 2019
Specificity of Metal Sensing: Iron and Manganese Homeostasis in Bacillus subtilis journal August 2014
Identification and Genomic Analysis of Transcription Factors in Archaeal Genomes Exemplifies Their Functional Architecture and Evolutionary Origin journal February 2010
A systems view of haloarchaeal strategies to withstand stress from transition metals journal July 2006
Identification of Mutations in Laboratory-Evolved Microbes from Next-Generation Sequencing Data Using breseq book January 2014
A Statistical Framework for the Analysis of ChIP-Seq Data journal September 2011
Genetic and biophysical studies of diphtheria toxin repressor (DtxR) and the hyperactive mutant DtxR(E175K) support a multistep model of activation journal February 2004
A precious metal: Iron, an essential nutrient for all cells journal March 2006
Introducing the ArsR-Regulated Arsenic Stimulon journal March 2021
The NRAMP proteins of Salmonella typhimurium and Escherichia coli are selective manganese transporters involved in the response to reactive oxygen journal June 2000
Transcriptional Regulation in Archaea: From Individual Genes to Global Regulatory Networks journal November 2017
Metalloid Resistance Mechanisms in Prokaryotes journal January 1998
A Regulatory Hierarchy Controls the Dynamic Transcriptional Response to Extreme Oxidative Stress in Archaea journal January 2015
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 journal December 2014
Temporal Study of the Microbial Diversity of the North Arm of Great Salt Lake, Utah, U.S. journal July 2015
Transposon Insertion Mutagenesis for Archaeal Gene Discovery book October 2016
GlpR Represses Fructose and Glucose Metabolic Enzymes at the Level of Transcription in the Haloarchaeon Haloferax volcanii journal October 2010