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PreprintCC BYbioRxiv

H-NS silences antiviral immunity through 3D chromatin compaction

1 more authors
  1. 1Center for Bio- and Medical Technologies, Moscow, Russia

Abstract

Bacterial antiviral immunity systems can be toxic to their hosts and must be tightly regulated. Immunity genes are often encoded by AT-rich mobile genetic elements subjected to silencing by nucleoid binding protein H-NS. Using RNA-seq, ChIP-seq, and chromosome 3D reconstruction with Micro-C, we find that H-NS binds and compacts bacterial immunity loci. H-NS deletion reveals anti-phage activity in model Escherichia coli strains generally considered phage-sensitive. Extending this approach to environmental isolates, we show that removal of H-NS silencing enhances defense, allowing bacteria to restrict phages with anti-defense proteins. We also discover Madara, a novel immunity system that complements the co-regulated BREX defense. Our results establish H-NS as a master regulator of bacterial immunity and highlight the importance of expression levels for anti-phage activity in native hosts.

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BibTeX
@misc{khvostikov2026silences,
  title = {{H-NS silences antiviral immunity through 3D chromatin compaction}},
  author = {T. Khvostikov and P. Iarema and A. Gavrilov and I. Shamovsky and V. Epshtein and A. Andriianov and P. Baikuzina and E. Shagimardanova and D. Senko and T. K. Wood and K. Severinov and E. Nudler and A. Isaev},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.05.749240},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.05.749240v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - H-NS silences antiviral immunity through 3D chromatin compaction
AU  - T. Khvostikov
AU  - P. Iarema
AU  - A. Gavrilov
AU  - I. Shamovsky
AU  - V. Epshtein
AU  - A. Andriianov
AU  - P. Baikuzina
AU  - E. Shagimardanova
AU  - D. Senko
AU  - T. K. Wood
AU  - K. Severinov
AU  - E. Nudler
AU  - A. Isaev
PY  - 2026
DA  - 2026/09/05
PB  - bioRxiv
DO  - 10.64898/2026.09.05.749240
UR  - https://www.biorxiv.org/content/10.64898/2026.09.05.749240v1
AB  - Bacterial antiviral immunity systems can be toxic to their hosts and must be tightly regulated. Immunity genes are often encoded by AT-rich mobile genetic elements subjected to silencing by nucleoid binding protein H-NS. Using RNA-seq, ChIP-seq, and chromosome 3D reconstruction with Micro-C, we find that H-NS binds and compacts bacterial immunity loci. H-NS deletion reveals anti-phage activity in model Escherichia coli strains generally considered phage-sensitive. Extending this approach to environmental isolates, we show that removal of H-NS silencing enhances defense, allowing bacteria to restrict phages with anti-defense proteins. We also discover Madara, a novel immunity system that complements the co-regulated BREX defense. Our results establish H-NS as a master regulator of bacterial immunity and highlight the importance of expression levels for anti-phage activity in native hosts.
ER  -