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The developmental regulator MtrA binds GlnR boxes and represses nitrogen metabolism genes in Streptomyces coelicolor
Author(s) -
Zhu Yanping,
Zhang Peipei,
Zhang Jing,
Xu Wenhao,
Wang Xinyuan,
Wu Lili,
Sheng Duohong,
Ma Wei,
Cao Guangxiang,
Chen Xiulan,
Lu Yinhua,
Zhang YuZhong,
Pang Xiuhua
Publication year - 2019
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14252
Subject(s) - biology , streptomyces coelicolor , gene , transcription factor , promoter , repressor , regulation of gene expression , genetics , microbiology and biotechnology , gene expression , mutant
Summary In Streptomyces , GlnR is an activator protein that activates nitrogen‐assimilation genes under nitrogen‐limiting conditions. However, less is known regarding the regulation of these genes under nitrogen‐rich conditions. We determined that the developmental regulator MtrA represses nitrogen‐assimilation genes in nitrogen‐rich media and that it competes with GlnR for binding to GlnR boxes. The GlnR boxes upstream of multiple nitrogen genes, such as amtB , were confirmed as MtrA binding sites in vitro by electrophoretic mobility shift assays and in vivo by ChIP‐qPCR analysis. Transcriptional analysis indicated that, on nutrient‐rich medium, MtrA profoundly repressed expression of nitrogen‐associated genes, indicating opposing roles for MtrA and GlnR in the control of nitrogen metabolism. Using in vitro and in vivo analysis, we also showed that glnR is itself a direct target of MtrA and that MtrA represses glnR transcription. We further demonstrated functional conservation of MtrA homologues in the recognition of GlnR boxes upstream of nitrogen genes from different actinobacterial species. As mtrA and glnR are widespread among actinomycetes, this mechanism of potential competitive control over nitrogen metabolism genes may be common in this group, adding a major new layer of complexity to the known regulatory network for nitrogen metabolism in Streptomyces and related species.