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

Award Number: R01GM147795
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Biomedical Research and Research Training	001	2	1/9/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Biomedical Research and Research Training	000	2	1/9/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $424,945 )
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Biomedical Research and Research Training	002	2	9/4/2024	SUPPLEMENT FOR EXPANSION	$108,636
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Biomedical Research and Research Training	000	2	1/10/2024	NON-COMPETING CONTINUATION	$284,678
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Biomedical Research and Research Training	001	2	6/24/2024	NON-COMPETING CONTINUATION	$31,631
														Subtotal = $424,945

Issue Date FY: 2023 ( Subtotal = $316,309 )
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Biomedical Research and Research Training	000	1	3/22/2023	NEW	$316,309
														Subtotal = $316,309

Grand Total All Awards = $741,254

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

Award Number: R01GM147795

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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