Abstract
BackgroundNdgR is an IclR-type transcription factor that regulates leucine biosynthesis and other metabolic pathways in Streptomyces coelicolor. Recent study revealed that NdgR is one of the regulatory targets of SigR, an oxidative stress response sigma factor, suggesting that the NdgR plays an important physiological role in response to environmental stresses. Although the regulatory functions of NdgR were partly characterized, determination of its regulon is required for better understanding of the transcriptional regulatory network related with the oxidative stress response.ResultsWe determined genome-wide binding loci of NdgR by using chromatin immunoprecipitation coupled with sequencing (ChIP-seq) and explored its physiological roles. The ChIP-seq profiles revealed 19 direct binding loci with a 15-bp imperfect palindromic motif, including 34 genes in their transcription units. Most genes in branched-chain amino acid and cysteine biosynthesis pathways were involved in the NdgR regulon. We proved that ndgR is induced by SigR under the thiol oxidation, and that an ndgR mutant strain is sensitive to the thiol oxidizing agent, diamide. Through the expression test of NdgR and the target genes for NdgR under diamide treatment, regulatory motifs were suggested. Interestingly, NdgR constitutes two regulatory motifs, coherent and incoherent feed-forward loops (FFL), in order to control its regulon under the diamide treatment. Using the regulatory motifs, NdgR regulates cysteine biosynthesis in response to thiol oxidative stress, enabling cells to maintain sulfur assimilation with homeostasis under stress conditions.ConclusionsOur analysis revealed that NdgR is a global transcriptional regulator involved in the regulation of branched-chain amino acids biosynthesis and sulphur assimilation. The identification of the NdgR regulon broadens our knowledge regarding complex regulatory networks governing amino acid biosynthesis in the context of stress responses in S. coelicolor.
Highlights
NdgR is an IclR-type transcription factor that regulates leucine biosynthesis and other metabolic pathways in Streptomyces coelicolor
We found that NdgR directly regulates 34 genes that are involved in the synthesis of Branched-chain amino acid (BCAA) and cysteine using 19 regulatory binding sites
We confirmed that SigR, an oxidative stress response sigma factor, induces NdgR in response to thiol oxidative stress induced by diamide treatment
Summary
NdgR is an IclR-type transcription factor that regulates leucine biosynthesis and other metabolic pathways in Streptomyces coelicolor. Streptomycetes are abundant and ubiquitous soil bacteria that are prolific producers of more than two-thirds of natural antibiotics used in the pharmaceutical industry They have complex regulatory systems for morphological differentiation in response to environmental or nutritional conditions. Genome sequences of this genus support the. The IclR proteins bind their cognate promoters as dimers or as a dimer of dimers with a helix-turn-helix DNA binding motif in the N-terminal domain. The members of this family are known to do repression, activation, or serve as dual-function regulators [4]. Members of the IclR family control a diverse array of genes whose products are involved in glyoxylate shunt in Enterobacteriaceae [7,8], multidrug resistance [9], degradation of aromatics [10,11,12], inactivation of quorum-sensing signals [13], and determinants of plant pathogenicity and sporulation [14]
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