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Mechanism of Heterochromatin Assembly and epigenetic inheritance

Award Number: R35GM126910
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/07/2018
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Mechanism of Heterochromatin Assembly and epigenetic inheritance - Project Summary Covalent modifications of histones, such as acetylation, methylation, phosphorylation, and ubiquitylation, are essential for regulating chromatin structure and function and defective histone modifications have causal roles in numerous developmental disorders and diseases. Our long-term goal is to use fission yeast heterochromatin assembly as an experimental model to study how diverse histone modification activities are coordinated to initiate different gene expression states and how these states are epigenetically inherited. Heterochromatin preferentially assembles at repetitive DNA elements, and it is essential for regulating gene expression and maintaining genome integrity. The formation of heterochromatin is critically dependent on the methylation of H3 lysine 9 (H3K9me). Interestingly, the activities of H3K9 methyltransferases are stimulated by the ubiquitylation of H3 lysine 14 (H3K14ub), although the mechanism is poorly understood. We will examine how H3K14ub stimulates H3K9 methyltransferases and how H3K14ub is regulated in vivo to aid heterochromatin assembly. Heterochromatin is also a great model to study chromatin-based mechanisms of epigenetic inheritance. An important unresolved question is how parental histones carrying modifications are deposited onto newly synthesized DNA during the S phase of the cell cycle to direct the duplication of these modifications on daughter chromatids. We developed eSPAN (enrichment of Sequencing Protein-Associated Nascent DNA) in fission yeast, which allows us to measure the segregation of parental histones on daughter DNA strands. We will integrate this new genomic tool and traditional genetic approaches to examine mechanisms that regulate the segregation of parental histones and how they contribute to epigenetic inheritance. Together, these studies will address fundamental questions about how histone modifications are regulated and inherited, and how their dysregulation contributes to human diseases.


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 TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	000	7	11/6/2024	NON-COMPETING CONTINUATION	$0
2025	2023	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	003	6	12/18/2024	COMPETING CONTINUATION	$101,056
2025	2022	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	001	5	12/18/2024	NON-COMPETING CONTINUATION	-$97,134
2025	2022	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	002	4	12/18/2024	SUPPLEMENT FOR EXPANSION	-$3,922
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $439,416 )
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	000	7	7/10/2024	NON-COMPETING CONTINUATION	$439,416
														Subtotal = $439,416

Issue Date FY: 2023 ( Subtotal = $412,086 )
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	202 LOW LIBRARY 535 W 116 ST MC 4309,	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	000	6	7/28/2023	COMPETING CONTINUATION	$412,086
														Subtotal = $412,086

Issue Date FY: 2022 ( Subtotal = $410,779 )
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	202 LOW LIBRARY 535 W 116 ST MC 4309,	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	000	4	5/27/2022	SUPPLEMENT FOR EXPANSION	$15,943
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	202 LOW LIBRARY 535 W 116 ST MC 4309,	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	001	5	7/21/2022	NON-COMPETING CONTINUATION	$394,836
														Subtotal = $410,779

Issue Date FY: 2021 ( Subtotal = $394,836 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	116TH AND BDWY	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	000	4	7/27/2021	NON-COMPETING CONTINUATION	$394,836
														Subtotal = $394,836

Issue Date FY: 2020 ( Subtotal = $453,101 )
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	116TH AND BDWY	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	002	3	7/17/2020	NON-COMPETING CONTINUATION	$394,836
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	116TH AND BDWY	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	001	2	6/15/2020	SUPPLEMENT FOR EXPANSION	$45,190
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	116TH AND BDWY	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	000	2	6/1/2020	SUPPLEMENT FOR EXPANSION	$13,075
														Subtotal = $453,101

Issue Date FY: 2019 ( Subtotal = $394,836 )
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	116TH AND BDWY	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	000	2	7/9/2019	NON-COMPETING CONTINUATION	$394,836
														Subtotal = $394,836

Issue Date FY: 2018 ( Subtotal = $417,733 )
2018	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	116TH AND BDWY	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	001	1	8/13/2018	NEW	$4,766
2018	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	116TH AND BDWY	NEW YORK	NY	10027	NEW YORK	USA	Biomedical Research and Research Training	000	1	8/7/2018	NEW	$412,967
														Subtotal = $417,733

Grand Total All Awards = $2,922,787

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Mechanism of Heterochromatin Assembly and epigenetic inheritance

Award Number: R35GM126910

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/07/2018

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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