title: A regulatory hierarchy controls the dynamic transcriptional response to extreme oxidative stress in archaea.
abstract: Networks of interacting transcription factors are central to the regulation of cellular responses to abiotic stress. Although the architecture of many such networks has been mapped, their dynamic function remains unclear. Here we address this challenge in archaea, microorganisms possessing transcription factors that resemble those of both eukaryotes and bacteria. Using genome-wide DNA binding location analysis integrated with gene expression and cell physiological data, we demonstrate that a bacterial-type transcription factor (TF), called RosR, and five TFIIB proteins, homologs of eukaryotic TFs, combinatorially regulate over 100 target genes important for the response to extremely high levels of peroxide. These genes include 20 other transcription factors and oxidative damage repair genes. RosR promoter occupancy is surprisingly dynamic, with the pattern of target gene expression during the transition from rapid growth to stress correlating strongly with the pattern of dynamic binding. We conclude that a hierarchical regulatory network orchestrated by TFs of hybrid lineage enables dynamic response and survival under extreme stress in archaea. This raises questions regarding the evolutionary trajectory of gene networks in response to stress.
authors.affiliation: Computational Biology and Bioinformatics Graduate Program, Duke University, Durham, North Carolina, United States of America; Biology Department, Duke University, Durham, North Carolina, United States of America.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Tonner
authors.affiliation: Biology Department, Duke University, Durham, North Carolina, United States of America.
authors.forename: Adrianne M C
authors.initials: AM
authors.lastname: Pittman
authors.affiliation: Biology Department, Duke University, Durham, North Carolina, United States of America.
authors.forename: Jordan G
authors.initials: JG
authors.lastname: Gulli
authors.affiliation: Biology Department, Duke University, Durham, North Carolina, United States of America.
authors.forename: Kriti
authors.initials: K
authors.lastname: Sharma
authors.affiliation: Computational Biology and Bioinformatics Graduate Program, Duke University, Durham, North Carolina, United States of America; Biology Department, Duke University, Durham, North Carolina, United States of America; Center for Systems Biology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Schmid
mesh_terms: D001105:Archaea / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D059372:Nucleotide Motifs / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics*; D035581:Transcription Factor TFIIB / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D035581:Transcription Factor TFIIB