Bacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversity
Year: 2024
Type: article
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. Bacteroides strains have multiple operons for biosynthesis of diverse capsular polysaccharides, but most cells express only one operon at a time due to tight regulation of transcription elongation by locus-specific UpxY and UpxZ proteins. Here, Saba et al. provide insight into the mechanisms by which UpxY distinguishes among cognate operons and how UpxZ inhibits only noncognate UpxY proteins.
Source: Nature Communications
Institutions: University of Wisconsin–Madison, University of Chicago
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: U.S. Department of Energy, U.S. Department of Health and Human Services, U.S. Department of Agriculture, University of Chicago, National Institutes of Health, Office of Science, Agricultural Research Service, Great Lakes Bioenergy Research Center, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Biological and Environmental Research
Awards: G1377182212, G1507877962, G1625130784, G1648283888, Single-cell elucidation of transcriptional regulatory mechanisms that govern cell surface variation of the human symbiotic bacteria Bacteroidetes, G1855443249, G1893268942, G2816542096, G2855515306, G3973886547, G3981254544, GREAT LAKES BIOENERGY RESEARCH CENTER, Biotechnology Training Program, G455569901, Diversity Supplement to Structure/Function of Transcription Complex Regulation to Support Predoctoral Student Christiana Binkley, Predoctoral Training Program in Genetics, G6198588377, G7350903426, G7457969771, G862408327, GREAT LAKES BIOENERGY RESEARCH CENTER, G9000008649, G9000026212, G9000029677, G9000078774, G9000171058, G9000331062, Biotechnology Training Program, Protective mechanisms of the gut Bacteroidales
OpenAlex ID: W4405894685