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This study used ChIP-seq and DNase I footprinting to map the genome-wide binding sites of CosR, an essential transcriptional regulator in the food-borne pathogen Campylobacter jejuni. The researchers identified a bipartite DNA recognition motif and found that CosR primarily binds at promoters to control genes involved in translation and transcription, representing core cellular processes. Oxidative stress caused differential changes in CosR binding across the genome, with reduced occupancy at translation-related promoters but increased binding at other targets, revealing redox-responsive regulatory remodeling.
Why it matters
Understanding how CosR regulates essential bacterial processes and responds to oxidative stress could inform strategies to combat C. jejuni infections, which are a leading cause of bacterial gastroenteritis worldwide. The findings reveal potential therapeutic targets by identifying how this pathogen coordinates core metabolism with environmental stress responses.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
CosR is an essential OmpR-family transcriptional regulator of Campylobacter jejuni, but its direct regulon and DNA-binding properties in vivo remain poorly defined. Here, we used ChIP-seq with a functional chromosomal CosR::3xFLAG allele to define the genome-wide CosR-binding landscape. CosR binding was strongly enriched at promoters and accumulated around transcription start sites, consistent with a primary role in transcriptional control. Functional analysis of promoter-bound targets revealed significant enrichment for translation- and transcription-related functions, identifying CosR as a regulator of core cellular processes. Motif analysis of summit-centered ChIP-seq regions identified a CosR-associated bipartite sequence signature characterized by TTAA-like elements separated by an A/T-rich spacer. DNase I footprinting confirmed direct promoter binding at nucleotide resolution and revealed heterogeneous architectures, including single, multipartite, and bidirectional binding arrangements. A footprint-derived motif was significantly similar to the ChIP-derived motif, supporting a shared recognition signature across in vivo-enriched regions and in vitro-protected segments. Footprinting also validated binding at non-coding RNA promoters and at the cosR promoter, indicating autoregulation. Hydrogen peroxide treatment differentially remodeled CosR promoter occupancy in vivo, reducing binding at translation-associated promoters while increasing enrichment at other targets. Redox-dependent footprinting showed that oxidative conditions directly impaired CosR binding at selected promoters, consistent with previously reported C218-dependent redox modulation. Despite these opposite occupancy patterns, most tested transcripts decreased after oxidative stress, indicating that CosR redox responsiveness is integrated with broader stress-dependent regulatory inputs. Together, these data define CosR as a condition-responsive regulator linking promoter recognition, core physiology and oxidative-stress-associated transcriptional remodeling.
Source: Genome-wide definition of the CosR regulon and DNA-binding properties in Campylobacter jejuni