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PreprintCC BYbioRxiv

Arc represses gene expression in IS605-family transposons

  1. 1Columbia University

Abstract

Bacterial insertion sequences (IS) are compact transposable elements that encode proteins required for their mobility and maintenance, yet many also encode accessory proteins with poorly understood functions. For example, IS605-family elements often encode a transposase called TnpA and an RNA-guided nuclease called TnpB that supports transposon maintenance, alongside an additional ribbon-helix-helix protein named Arc. Though the roles of TnpA and TnpB have been extensively studied in recent years, the enigmatic function of Arc has not been investigated. Here, we show that Arc acts as a transcriptional repressor to directly bind the transposon's native promoter sequence regulating TnpA and TnpB gene expression. By systematically testing Arc-containing IS605 elements, we identified a conserved binding pattern at intergenic transposon sequences neighboring protein-coding genes through chromatin immunoprecipitation and sequencing analyses. We then used fluorescence reporter assays and demonstrated that these intergenic sequences function as strong promoters, and that the presence of Arc dramatically reduces their gene expression. Together, these findings identify Arc as a transposon-encoded transcriptional repressor, revealing a regulatory layer that may promote long-term persistence of IS605-family elements by keeping their activity in check. The widespread association of Arc homologs with diverse mobile elements and cellular genes suggests that these compact regulators may more broadly restrain the expression of neighboring genetic machinery across varied genomic contexts.

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BibTeX
@misc{moon2026represses,
  title = {{Arc represses gene expression in IS605-family transposons}},
  author = {Y. D. Moon and R. Zedaveinyte and T. Wiegand and S. H. Sternberg},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.24.754181},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.24.754181v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Arc represses gene expression in IS605-family transposons
AU  - Y. D. Moon
AU  - R. Zedaveinyte
AU  - T. Wiegand
AU  - S. H. Sternberg
PY  - 2026
DA  - 2026/09/24
PB  - bioRxiv
DO  - 10.64898/2026.09.24.754181
UR  - https://www.biorxiv.org/content/10.64898/2026.09.24.754181v1
AB  - Bacterial insertion sequences (IS) are compact transposable elements that encode proteins required for their mobility and maintenance, yet many also encode accessory proteins with poorly understood functions. For example, IS605-family elements often encode a transposase called TnpA and an RNA-guided nuclease called TnpB that supports transposon maintenance, alongside an additional ribbon-helix-helix protein named Arc. Though the roles of TnpA and TnpB have been extensively studied in recent years, the enigmatic function of Arc has not been investigated. Here, we show that Arc acts as a transcriptional repressor to directly bind the transposon's native promoter sequence regulating TnpA and TnpB gene expression. By systematically testing Arc-containing IS605 elements, we identified a conserved binding pattern at intergenic transposon sequences neighboring protein-coding genes through chromatin immunoprecipitation and sequencing analyses. We then used fluorescence reporter assays and demonstrated that these intergenic sequences function as strong promoters, and that the presence of Arc dramatically reduces their gene expression. Together, these findings identify Arc as a transposon-encoded transcriptional repressor, revealing a regulatory layer that may promote long-term persistence of IS605-family elements by keeping their activity in check. The widespread association of Arc homologs with diverse mobile elements and cellular genes suggests that these compact regulators may more broadly restrain the expression of neighboring genetic machinery across varied genomic contexts.
ER  -