# The Ies6 subunit is essential for INO80-mediated nucleosome organization

## TL;DR

The Ies6 subunit is crucial for organizing nucleosomes in yeast, and its absence disrupts chromatin structure and interacts with another remodeler.

## Contribution

This study reveals the essential role of Ies6 in INO80-mediated nucleosome organization and its functional redundancy with ISW2.

## Key findings

- Ies6 deletion reduces nucleosome spacing by 3 bp and disrupts nucleosome arrays.
- IES6 deletion is synthetically lethal with ISW2 deletion, showing functional overlap.
- INO80 binding directly correlates with Ies6's role in nucleosome organization.

## Abstract

ATP-dependent nucleosome remodelers of the INO80 family regulate chromatin by sliding, spacing and positioning nucleosomes. The INO80 remodeler is organized into structural modules that regulate its remodeling activity. Here, we investigate the role of the Ies6 subunit within the Arp5-Ies6 module towards nucleosome positioning and spacing in Saccharomyces cerevisiae. We show that Ies6 is critical for establishing genome-wide nucleosome organization. Deletion of IES6 reduces nucleosome spacing by 3 bp and disrupts regular nucleosome arrays across most genes. Surprisingly, deletion of IES6 is synthetically lethal with the deletion of ISW2, a remodeler from the ISWI family, indicating functional redundancy in nucleosome organization. Notably, INO80 binding directly predicts the role of Ies6 in INO80-mediated nucleosome organization, whereas changes in gene expression do not correlate with altered nucleosome spacing or array regularity. Together, our results highlight the essential role of the Ies6 subunit in INO80-mediated chromatin organization.

The online version contains supplementary material available at 10.1038/s41598-026-40504-8.