Bacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversity
Abstract The genomes of human gut bacteria in the genus Bacteroides include numerous operons for biosynthesis of diverse capsular polysaccharides (CPSs). The first two genes of each CPS operon encode a locus-specific paralog of transcription elongation factor NusG (called UpxY), which enhances trans...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55215-9 |
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| author | Jason Saba Katia Flores Bailey Marshall Michael D. Engstrom Yikai Peng Atharv S. Garje Laurie E. Comstock Robert Landick |
| author_facet | Jason Saba Katia Flores Bailey Marshall Michael D. Engstrom Yikai Peng Atharv S. Garje Laurie E. Comstock Robert Landick |
| author_sort | Jason Saba |
| collection | DOAJ |
| description | Abstract The genomes of human gut bacteria in the genus Bacteroides include numerous operons for biosynthesis of diverse capsular polysaccharides (CPSs). The first two genes of each CPS operon encode a locus-specific paralog of transcription elongation factor NusG (called UpxY), which enhances transcript elongation, and a UpxZ protein that inhibits noncognate UpxYs. This process, together with promoter inversions, ensures that a single CPS operon is transcribed in most cells. Here, we use in-vivo nascent-RNA sequencing and promoter-less in-vitro transcription (PIVoT) to show that UpxY recognizes a paused RNA polymerase via sequences in both the exposed non-template DNA and the upstream duplex DNA. UpxY association is aided by ‘pause-then-escape’ nascent RNA hairpins. UpxZ binds non-cognate UpxYs to directly inhibit UpxY association. This UpxY-UpxZ hierarchical regulatory program allows Bacteroides to generate subpopulations of cells producing diverse CPSs for optimal fitness. |
| format | Article |
| id | doaj-art-2d7443121d8c44f2a8928db149361fcd |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-2d7443121d8c44f2a8928db149361fcd2025-08-20T01:48:08ZengNature PortfolioNature Communications2041-17232024-12-0115111610.1038/s41467-024-55215-9Bacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversityJason Saba0Katia Flores1Bailey Marshall2Michael D. Engstrom3Yikai Peng4Atharv S. Garje5Laurie E. Comstock6Robert Landick7Department of Biochemistry, University of Wisconsin–MadisonDepartment of Microbiology, University of ChicagoDepartment of Biochemistry, University of Wisconsin–MadisonDepartment of Biochemistry, University of Wisconsin–MadisonDepartment of Biochemistry, University of Wisconsin–MadisonDepartment of Biochemistry, University of Wisconsin–MadisonDepartment of Microbiology, University of ChicagoDepartment of Biochemistry, University of Wisconsin–MadisonAbstract The genomes of human gut bacteria in the genus Bacteroides include numerous operons for biosynthesis of diverse capsular polysaccharides (CPSs). The first two genes of each CPS operon encode a locus-specific paralog of transcription elongation factor NusG (called UpxY), which enhances transcript elongation, and a UpxZ protein that inhibits noncognate UpxYs. This process, together with promoter inversions, ensures that a single CPS operon is transcribed in most cells. Here, we use in-vivo nascent-RNA sequencing and promoter-less in-vitro transcription (PIVoT) to show that UpxY recognizes a paused RNA polymerase via sequences in both the exposed non-template DNA and the upstream duplex DNA. UpxY association is aided by ‘pause-then-escape’ nascent RNA hairpins. UpxZ binds non-cognate UpxYs to directly inhibit UpxY association. This UpxY-UpxZ hierarchical regulatory program allows Bacteroides to generate subpopulations of cells producing diverse CPSs for optimal fitness.https://doi.org/10.1038/s41467-024-55215-9 |
| spellingShingle | Jason Saba Katia Flores Bailey Marshall Michael D. Engstrom Yikai Peng Atharv S. Garje Laurie E. Comstock Robert Landick Bacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversity Nature Communications |
| title | Bacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversity |
| title_full | Bacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversity |
| title_fullStr | Bacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversity |
| title_full_unstemmed | Bacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversity |
| title_short | Bacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversity |
| title_sort | bacteroides expand the functional versatility of a conserved transcription factor and transcribed dna to program capsule diversity |
| url | https://doi.org/10.1038/s41467-024-55215-9 |
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