# Uncovering the biomolecular function of the R-octasome--a nucleosome-like particle with only H3 and H4 histones

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $108,636

## Abstract

Abstract:
The chromatin landscape of eukaryotic cells is decorated with landmarks characterized by covalent
modifications and variant nucleoprotein structures. In this proposed project, we aim to investigate the
R-octasome, a nucleosome-like particles but with a core made up of four H3 and H4 histones. We
recently solved the cryo-EM structure of the R-octasome and detected its presence in yeast using in
vivo crosslinking techniques. However, the biological function of R-octasomes remains unknown.
Preliminary data suggest that R-octasomes are associated with the telomeric repeats. Using a mutant
that disrupts R-octasome formation, our data suggest that its integrity is crucial for sub-telomeric gene
silencing. We hypothesize that R-octasomes are integral components of telomeric heterochromatin.
We proposed three aims to further study the biological roles of the R-octasome. Aim 1: Develop a
methodology to purify native R-octasomes from yeast for biochemical, genomic, and structural
studies. Aim 2: Investigate the role of R-octasomes in telomeric gene silencing and their function as
substrates of ATP-dependent chromatin remodelers. Aim 3: Explore the role of R-octasomes in
higher-order chromatin organization. Our structural data suggest that R-octasomes can nucleate the
concatenation of additional H3 and H4 histones. Overall, the outcome of this research will provide
new insights into how eukaryotes use the highly conserved H3 and H4 as multi-functional substrates
to modulate genomic functions.

## Key facts

- **NIH application ID:** 11097649
- **Project number:** 3R01GM147795-02S1
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Edward E Luk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $108,636
- **Award type:** 3
- **Project period:** 2023-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11097649

## Citation

> US National Institutes of Health, RePORTER application 11097649, Uncovering the biomolecular function of the R-octasome--a nucleosome-like particle with only H3 and H4 histones (3R01GM147795-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11097649. Licensed CC0.

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