Sequence-dependent binding modes of INO80 control +1 nucleosome positioning

Abstract

Cellular self-organisation counteracts entropy at the expenditure of energy. In case of the first level of nuclear DNA organisation, this relates to regular nucleosome arrays and interspaced nucleosome-depleted regions (NDRs), for example at promoters or replication origins. The organisation of nucleosomes as building blocks of chromatin is orchestrated by the collective activities of ATP-dependent chromatin remodellers. Yet, how remodellers achieve positional specificity, in particular regarding the promoter-proximal +1 nucleosomes, remains unclear. Here, we show that the S. cerevisiae chromatin remodeller INO80 unexpectedly distinguishes DNA sequence asymmetry within the +1 nucleosome of the SWH1 gene through distinct inhibited and active nucleosome-binding modes. In structural and biochemical analyses of INO80 on nucleosomes with the endogenous sequence, we identified an inhibited binding mode where the entire INO80 remodelling unit flipped on the +1 nucleosome. INO80 adopted this remodelling-incompetent binding mode when facing the promoter, but a remodelling-competent mode when facing the gene body. This directional read-out of intra-nucleosomal DNA sequence asymmetry, together with extranucleosomal NDR sequence features, prevented nucleosome sliding into the NDR while permitting array formation over the gene. Our work shows how DNA features contribute to ATP-dependent self-organisation of promoter chromatin by INO80.

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Cite

BibTeX RIS

BibTeX

@misc{likhodeeva2026sequencedependent,
  title = {{Sequence-dependent binding modes of INO80 control +1 nucleosome positioning}},
  author = {M. Likhodeeva and A. Brem and A. Lopez-Francos and D. Shabani and F. Därr and D. Kostrewa and K. Lammens and M. Moldt and O. Fettscher and B. Bartholomew and P. Korber and K.-P. Hopfner},
  howpublished = {bioRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.12.744421},
  url = {https://www.biorxiv.org/content/10.64898/2026.08.12.744421v2},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Sequence-dependent binding modes of INO80 control +1 nucleosome positioning
AU  - M. Likhodeeva
AU  - A. Brem
AU  - A. Lopez-Francos
AU  - D. Shabani
AU  - F. Därr
AU  - D. Kostrewa
AU  - K. Lammens
AU  - M. Moldt
AU  - O. Fettscher
AU  - B. Bartholomew
AU  - P. Korber
AU  - K.-P. Hopfner
PY  - 2026
DA  - 2026/08/12
PB  - bioRxiv
DO  - 10.64898/2026.08.12.744421
UR  - https://www.biorxiv.org/content/10.64898/2026.08.12.744421v2
AB  - Cellular self-organisation counteracts entropy at the expenditure of energy. In case of the first level of nuclear DNA organisation, this relates to regular nucleosome arrays and interspaced nucleosome-depleted regions (NDRs), for example at promoters or replication origins. The organisation of nucleosomes as building blocks of chromatin is orchestrated by the collective activities of ATP-dependent chromatin remodellers. Yet, how remodellers achieve positional specificity, in particular regarding the promoter-proximal +1 nucleosomes, remains unclear. Here, we show that the S. cerevisiae chromatin remodeller INO80 unexpectedly distinguishes DNA sequence asymmetry within the +1 nucleosome of the SWH1 gene through distinct inhibited and active nucleosome-binding modes. In structural and biochemical analyses of INO80 on nucleosomes with the endogenous sequence, we identified an inhibited binding mode where the entire INO80 remodelling unit flipped on the +1 nucleosome. INO80 adopted this remodelling-incompetent binding mode when facing the promoter, but a remodelling-competent mode when facing the gene body. This directional read-out of intra-nucleosomal DNA sequence asymmetry, together with extranucleosomal NDR sequence features, prevented nucleosome sliding into the NDR while permitting array formation over the gene. Our work shows how DNA features contribute to ATP-dependent self-organisation of promoter chromatin by INO80.
ER  -

Abstract

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