{"doi":"10.1093/nar/gkad088","title":"Localized modulation of DNA supercoiling, triggered by the <i>Shigella</i> anti-silencer VirB, is sufficient to relieve H-NS-mediated silencing","abstract":"In Bacteria, nucleoid structuring proteins govern nucleoid dynamics and regulate transcription. In Shigella spp., at ≤30°C, the histone-like nucleoid structuring protein (H-NS) transcriptionally silences many genes on the large virulence plasmid. Upon a switch to 37°C, VirB, a DNA binding protein and key transcriptional regulator of Shigella virulence, is produced. VirB functions to counter H-NS-mediated silencing in a process called transcriptional anti-silencing. Here, we show that VirB mediates a loss of negative DNA supercoils from our plasmid-borne, VirB-regulated PicsP-lacZ reporter in vivo. The changes are not caused by a VirB-dependent increase in transcription, nor do they require the presence of H-NS. Instead, the VirB-dependent change in DNA supercoiling requires the interaction of VirB with its DNA binding site, a critical first step in VirB-dependent gene regulation. Using two complementary approaches, we show that VirB:DNA interactions in vitro introduce positive supercoils in plasmid DNA. Subsequently, by exploiting transcription-coupled DNA supercoiling, we reveal that a localized loss of negative supercoils is sufficient to alleviate H-NS-mediated transcriptional silencing independently of VirB. Together, our findings provide novel insight into VirB, a central regulator of Shigella virulence and, more broadly, a molecular mechanism that offsets H-NS-dependent silencing of transcription in bacteria.","journal":"Nucleic Acids Research","year":2023,"id":326063,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1044493,"name":"Monika M. A. Karney","orcid":"0000-0002-8863-7676","position":1,"is_corresponding":false},{"id":1044494,"name":"Taylor M. Gerson","orcid":"0009-0004-8794-2742","position":2,"is_corresponding":false},{"id":531967,"name":"Alexander Karabachev","orcid":"0000-0003-1747-1194","position":3,"is_corresponding":false},{"id":874058,"name":"Juan Carlos Duhart","orcid":"0000-0002-1878-251X","position":4,"is_corresponding":false},{"id":1044495,"name":"Joy A. McKenna","orcid":"0000-0002-6742-6511","position":5,"is_corresponding":false},{"id":1044496,"name":"Helen J. Wing","orcid":"0000-0003-0123-5568","position":6,"is_corresponding":false},{"id":558092,"name":"Michael A. Picker","orcid":null,"position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T01:08:28.266998Z","pmid":"36794722","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}