Limits...
Intermediate Levels of Bacillus subtilis CodY Activity Are Required for Derepression of the Branched-Chain Amino Acid Permease, BraB.

Belitsky BR, Brinsmade SR, Sonenshein AL - PLoS Genet. (2015)

Bottom Line: However, under conditions of reduced CodY activity, CodY-mediated repression was relieved to a greater extent than ScoC-mediated repression was increased, leading to elevated braB expression.We conclude that restricting increased expression of braB to conditions of moderate nutrient limitation is the raison d'être of the feed-forward regulatory loop formed by CodY and ScoC at the braB promoter.The increase in BraB expression only at intermediate activities of CodY may facilitate the uptake of BCAA when they are not in excess but prevent unneeded BraB synthesis when other BCAA transporters are active.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.

ABSTRACT
The global transcriptional regulator, CodY, binds strongly to the regulatory region of the braB gene, which encodes a Bacillus subtilis branched-chain amino acid (BCAA) permease. However, under conditions that maximize CodY activity, braB expression was similar in wild-type and codY mutant cells. Nonetheless, expression from the braB promoter was significantly elevated in cells containing partially active mutant versions of CodY or in wild-type cells under growth conditions leading to intermediate levels of CodY activity. This novel pattern of regulation was shown to be due to two opposing mechanisms, negative and positive, by which CodY affects braB expression. A strong CodY-binding site located downstream of the transcription start point conferred negative regulation by direct interaction with CodY. Additionally, sequences upstream and downstream of the promoter were required for repression by a second pleiotropic B. subtilis regulator, ScoC, whose own expression is repressed by CodY. ScoC-mediated repression of braB in codY mutants cells was as efficient as direct, CodY-mediated repression in wild-type cells under conditions of high CodY activity. However, under conditions of reduced CodY activity, CodY-mediated repression was relieved to a greater extent than ScoC-mediated repression was increased, leading to elevated braB expression. We conclude that restricting increased expression of braB to conditions of moderate nutrient limitation is the raison d'ĂȘtre of the feed-forward regulatory loop formed by CodY and ScoC at the braB promoter. The increase in BraB expression only at intermediate activities of CodY may facilitate the uptake of BCAA when they are not in excess but prevent unneeded BraB synthesis when other BCAA transporters are active.

No MeSH data available.


A model of regulation of the braB promoter by the combined actions of CodY and ScoC.The sizes of the circles reflect the relative amount of the active form of each protein. The solid vertical lines indicate relatively strong effects on transcription. Dotted lines indicate relatively weak effects on transcription. The boldness of the horizontal arrows indicates the relative strength of transcription of the target genes.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4608796&req=5

pgen.1005600.g009: A model of regulation of the braB promoter by the combined actions of CodY and ScoC.The sizes of the circles reflect the relative amount of the active form of each protein. The solid vertical lines indicate relatively strong effects on transcription. Dotted lines indicate relatively weak effects on transcription. The boldness of the horizontal arrows indicates the relative strength of transcription of the target genes.

Mentions: Although previous analysis did not detect any significant regulation of braB by CodY, we now know that braB is subject to complex CodY-mediated regulation by which the protein acts both as a direct repressor and as an indirect positive regulator. The positive effect of CodY is mediated by its repression of the gene encoding a second repressor of braB, ScoC. As a result, braB expression only escapes repression under conditions (e.g., during growth in a medium containing multiple amino acids but lacking ILV) in which CodY activity is limited enough to prevent repression of braB, but high enough to maintain sufficient repression of scoC (Fig 9).


Intermediate Levels of Bacillus subtilis CodY Activity Are Required for Derepression of the Branched-Chain Amino Acid Permease, BraB.

Belitsky BR, Brinsmade SR, Sonenshein AL - PLoS Genet. (2015)

A model of regulation of the braB promoter by the combined actions of CodY and ScoC.The sizes of the circles reflect the relative amount of the active form of each protein. The solid vertical lines indicate relatively strong effects on transcription. Dotted lines indicate relatively weak effects on transcription. The boldness of the horizontal arrows indicates the relative strength of transcription of the target genes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608796&req=5

pgen.1005600.g009: A model of regulation of the braB promoter by the combined actions of CodY and ScoC.The sizes of the circles reflect the relative amount of the active form of each protein. The solid vertical lines indicate relatively strong effects on transcription. Dotted lines indicate relatively weak effects on transcription. The boldness of the horizontal arrows indicates the relative strength of transcription of the target genes.
Mentions: Although previous analysis did not detect any significant regulation of braB by CodY, we now know that braB is subject to complex CodY-mediated regulation by which the protein acts both as a direct repressor and as an indirect positive regulator. The positive effect of CodY is mediated by its repression of the gene encoding a second repressor of braB, ScoC. As a result, braB expression only escapes repression under conditions (e.g., during growth in a medium containing multiple amino acids but lacking ILV) in which CodY activity is limited enough to prevent repression of braB, but high enough to maintain sufficient repression of scoC (Fig 9).

Bottom Line: However, under conditions of reduced CodY activity, CodY-mediated repression was relieved to a greater extent than ScoC-mediated repression was increased, leading to elevated braB expression.We conclude that restricting increased expression of braB to conditions of moderate nutrient limitation is the raison d'être of the feed-forward regulatory loop formed by CodY and ScoC at the braB promoter.The increase in BraB expression only at intermediate activities of CodY may facilitate the uptake of BCAA when they are not in excess but prevent unneeded BraB synthesis when other BCAA transporters are active.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.

ABSTRACT
The global transcriptional regulator, CodY, binds strongly to the regulatory region of the braB gene, which encodes a Bacillus subtilis branched-chain amino acid (BCAA) permease. However, under conditions that maximize CodY activity, braB expression was similar in wild-type and codY mutant cells. Nonetheless, expression from the braB promoter was significantly elevated in cells containing partially active mutant versions of CodY or in wild-type cells under growth conditions leading to intermediate levels of CodY activity. This novel pattern of regulation was shown to be due to two opposing mechanisms, negative and positive, by which CodY affects braB expression. A strong CodY-binding site located downstream of the transcription start point conferred negative regulation by direct interaction with CodY. Additionally, sequences upstream and downstream of the promoter were required for repression by a second pleiotropic B. subtilis regulator, ScoC, whose own expression is repressed by CodY. ScoC-mediated repression of braB in codY mutants cells was as efficient as direct, CodY-mediated repression in wild-type cells under conditions of high CodY activity. However, under conditions of reduced CodY activity, CodY-mediated repression was relieved to a greater extent than ScoC-mediated repression was increased, leading to elevated braB expression. We conclude that restricting increased expression of braB to conditions of moderate nutrient limitation is the raison d'ĂȘtre of the feed-forward regulatory loop formed by CodY and ScoC at the braB promoter. The increase in BraB expression only at intermediate activities of CodY may facilitate the uptake of BCAA when they are not in excess but prevent unneeded BraB synthesis when other BCAA transporters are active.

No MeSH data available.