Single-residue variation in the nucleosome core reveals a regulatory hub for phenotypic innovation
- 1Gregor Mendel Institute
Abstract
Nucleosomes organize genomes and regulate DNA access, yet accumulating evidence suggests that their constituent histones may have functions beyond canonical chromatin regulation, but the breadth of such regulatory diversity remains unclear. Here, we used the six-residue loop 2 (L2) of H2A and H2A.Z to map, at single-residue resolution, how nucleosome-core variation reshapes cellular function. Genome-scale interaction mapping identified hundreds of regulatory connections spanning chromatin, as well as actin organization, endocytosis, and membrane trafficking. Interactions were residue-specific and differed between H2A and H2A.Z, revealing a regulatory landscape encoded by single residues. Transcriptome profiling showed limited expression changes and little overlap between differentially expressed genes and regulatory partners, indicating that non-chromatin connections are not readily explained by altered transcription. L2 substitutions also preferentially conferred benefits under cell wall and membrane stress. Thus, the nucleosome is linked to cellular-periphery functions beyond classical chromatin regulation, identifying histone variation as a source of phenotypic innovation.
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BibTeX
@misc{harvey2026singleresidue,
title = {{Single-residue variation in the nucleosome core reveals a regulatory hub for phenotypic innovation}},
author = {Z. H. Harvey and B. Gundinger and J. Y. Kok and K. M. Stevens and T. Warnecke and F. Berger},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.11.750863},
url = {https://www.biorxiv.org/content/10.64898/2026.09.11.750863v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Single-residue variation in the nucleosome core reveals a regulatory hub for phenotypic innovation
AU - Z. H. Harvey
AU - B. Gundinger
AU - J. Y. Kok
AU - K. M. Stevens
AU - T. Warnecke
AU - F. Berger
PY - 2026
DA - 2026/09/11
PB - bioRxiv
DO - 10.64898/2026.09.11.750863
UR - https://www.biorxiv.org/content/10.64898/2026.09.11.750863v1
AB - Nucleosomes organize genomes and regulate DNA access, yet accumulating evidence suggests that their constituent histones may have functions beyond canonical chromatin regulation, but the breadth of such regulatory diversity remains unclear. Here, we used the six-residue loop 2 (L2) of H2A and H2A.Z to map, at single-residue resolution, how nucleosome-core variation reshapes cellular function. Genome-scale interaction mapping identified hundreds of regulatory connections spanning chromatin, as well as actin organization, endocytosis, and membrane trafficking. Interactions were residue-specific and differed between H2A and H2A.Z, revealing a regulatory landscape encoded by single residues. Transcriptome profiling showed limited expression changes and little overlap between differentially expressed genes and regulatory partners, indicating that non-chromatin connections are not readily explained by altered transcription. L2 substitutions also preferentially conferred benefits under cell wall and membrane stress. Thus, the nucleosome is linked to cellular-periphery functions beyond classical chromatin regulation, identifying histone variation as a source of phenotypic innovation.
ER -