Different modes of engagement with the nucleosome acidic patch yield distinct functional outcomes

The nucleosome acidic patch is a hub of coordinated engagement by proteins that regulate genomic function. Here we report that <i>S. cerevisiae</i> Dot5 contains an arginine-rich HMGN-like motif that mediates nucleosome acidic patch binding and is required for the cell growth, DNA repair and heterochromatin defects exhibited when the protein is overexpressed. The heterologous expression of camelid single chain antibodies to the nucleosome acidic patch confers a similar range of phenotypes, with the most severe observed when an 'arginine-anchor' mode of binding analogous to many endogenous factors is employed. This highlights a delicate balance between nucleosome acidic patch interactors critical for normal cellular functions and dysregulated in disease.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-01-14
DOI
https://doi.org/10.64898/2026.01.14.699602
Primary Topic
Genomics and Chromatin Dynamics
Type
article
Field-Weighted Citation Impact
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article

Different modes of engagement with the nucleosome acidic patch yield distinct functional outcomes

Heather J. Folkwein, Nina Arslanovic, Jean‐Paul Armache, Jessica K. Tyler et al.
bioRxiv (Cold Spring Harbor Laboratory)
Genomics and Chromatin Dynamics
article

Different modes of engagement with the nucleosome acidic patch yield distinct functional outcomes

Heather J. Folkwein, Nina Arslanovic, Jean‐Paul Armache, Jessica K. Tyler, Ujani Chakraborty, Natalia Ledo Husby, George Kassavetis, Sabrina R. Hunt, Harrison A. Fuchs, J T Kadonaga, Rhiannon R. Aguilar, Keith E. Maier, laiba Kahn, Michael-Christopher Keogh, GRISEL L CRUZ BECERRA, Keith Maier, Noah Schomburg, Bryan Venters, Emma Saccone, Wen Sun
article en

Abstract

The nucleosome acidic patch is a hub of coordinated engagement by proteins that regulate genomic function. Here we report that <i>S. cerevisiae</i> Dot5 contains an arginine-rich HMGN-like motif that mediates nucleosome acidic patch binding and is required for the cell growth, DNA repair and heterochromatin defects exhibited when the protein is overexpressed. The heterologous expression of camelid single chain antibodies to the nucleosome acidic patch confers a similar range of phenotypes, with the most severe observed when an 'arginine-anchor' mode of binding analogous to many endogenous factors is employed. This highlights a delicate balance between nucleosome acidic patch interactors critical for normal cellular functions and dysregulated in disease.

bioRxiv (Cold Spring Harbor Laboratory)
Pennsylvania State University (US), Cornell University (US), University of California San Diego (US), EpiCypher (United States) (US), Weill Cornell Medicine (US)
Openalex Percentile: Top 88%
Genomics and Chromatin Dynamics
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Different modes of engagement with the nucleosome acidic patch yield distinct functional outcomes — Heather J. Folkwein, Nina Arslanovic, et al. · bioRxiv (Cold Spring Harbor Laboratory) (2026) | TGRS Research Map | TGRS