Conservation of thiol-oxidative stress responses regulated by SigR orthologues in actinomycetes.
Numerous thiol-reactive compounds cause oxidative stress where cells counteract by activation of survival strategies regulated by thiol-based sensors. In Streptomyces coelicolor, a model actinomycete, a sigma/antisigma pair SigR/RsrA controls the response to thiol-oxidative stress. To unravel its full physiological functions, chromatin immuno-precipitation combined with sequence and transcript analyses were employed to identify 108 SigR target genes in S. coelicolor and to predict orthologous regulons across actinomycetes. In addition to reported genes for thiol homeostasis, protein degradation and ribosome modulation, 64 additional operons were identified suggesting new functions of this global regulator. We demonstrate that SigR maintains the level and activity of the housekeeping sigma factor HrdB during thiol-oxidative stress, a novel strategy for stress responses. We also found that SigR defends cells against UV and thiol-reactive damages, in which repair UvrA takes a part. Using a refined SigR-binding sequence model, SigR orthologues and their targets were predicted in 42 actinomycetes. This revealed a conserved core set of SigR targets to function for thiol homeostasis, protein quality control, possible modulation of transcription and translation, flavin-mediated redox reactions, and Fe-S delivery. The composition of the SigR regulon reveals a robust conserved physiological mechanism to deal with thiol-oxidative stress from bacteria to human.
Laboratory of Molecular Microbiology, School of Biological Sciences, and Institute of Microbiology, Seoul National University, Seoul 151-742, Korea.
Min-Sik
MS
Kim
Yann S
YS
Dufour
Ji Sun
JS
Yoo
Yoo-Bok
YB
Cho
Joo-Hong
JH
Park
Gi-Baeg
GB
Nam
Hae Min
HM
Kim
Kang-Lok
KL
Lee
Timothy J
TJ
Donohue
Jung-Hye
JH
Roe
D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D050296:Microbial Viability / Q000187:drug effects; D018384:Oxidative Stress; D018085:Regulon; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D048372:Streptomyces coelicolor / Q000187:drug effects* / Q000502:physiology*; D013312:Stress, Physiological; D013438:Sulfhydryl Compounds / Q000633:toxicity*; D014157:Transcription Factors
D013438:Sulfhydryl Compounds; D014157:Transcription Factors