GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307027/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307027GEOGSEfalseOrientia tsutsugamushi Ank effectors target lamin A and chromatin to inhibit NF-kBIntracellular 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.2026/04/13GSE307027GSM9214448GSM9214449GSM9214451GSM9214450GSM9214453GSM921445220301307027Homo sapiens