{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307027/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307027"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Orientia tsutsugamushi Ank effectors target lamin A and chromatin to inhibit NF-kB","description":"Intracellular pathogens inhibit nuclear factor-κB (NF-κB), the key transcriptional regulator of antimicrobial responses, using incompletely defined mechanisms. NF-κB nuclear localization and gene accessibility is mediated by Ser22-phosphorylated lamin A/C (pSer22-lamin A/C). Here, we report that the obligate intracellular bacterium Orientia tsutsugamushi impairs NF-κB nuclear accumulation by targeting lamin A using a cohort of ankyrin repeat (AR)-containing effectors (Anks) that have a PRANC (pox proteins repeats of ankyrin C-terminal) domain. The Anks’ immunomodulatory capability relies on a hydrophilic peptide that binds lamin A and pSer22-lamin A. Positioning of this peptide in an a-helix between the AR and PRANC domains is functionally essential. O. tsutsugamushi and ectopically expressed Ank1, one of the NF-κB-inhibiting Anks, promote pSer22-lamin A localization to the nucleoplasm. Orientia also alters chromatin to a primarily closed state to limit accessibility at many sites including those regulated by lamin A/pSer22-lamin A along with NF-κB and its coactivator, adapter protein 1. Thus, O. tsutsugamushi synergistically modulates lamin A and chromatin accessibility to counteract NF-κB. These findings reveal a strategy by which an intracellular microbe subverts host immunity, reinforces the regulatory link between lamin A and NF-κB, and indicates that pSer22-lamin A activates NF-κB by increasing chromatin accessibility to it and its coactivators.","dates":{"publication":"2026/04/13"},"accession":"GSE307027","cross_references":{"GSM":["GSM9214448","GSM9214449","GSM9214451","GSM9214450","GSM9214453","GSM9214452"],"GPL":["20301"],"GSE":["307027"],"taxon":["Homo sapiens"]}}