Wednesday, January 15, 2025 1/15/2025

Epigenetic inheritance of heterochromatin

Award Number: R01GM072805
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary The long-term goal of this work is to understand how histone H3 lysine 9 methylation (H3K9me) and heterochromatic gene silencing are epigenetically inherited. Heterochromatin is a conserved feature of eukaryotic chromosmes and plays important roles in regulation of gene expression and maintenance of chromosome stability in organisms ranging from yeast to human. Using the fission yeast Schiozosaccharomyces pombe as a model organism, we recently demonstrated that ectopically induced domains of H3K9me and silencing can be epigenetically inherited in the absence of sequence-specific recruitment when the rate of H3K9me demethylation is reduced by deletion of the Epe1 anti-silencing factor. In addition, we have discovered that, in wildtype epe1+ cells, small noncoding RNAs (siRNAs) or transcription factor binding sites play critical roles in epigenetic maintenance of H3K9me. More recently, we have uncovered roles for an RNAi-independent RNA decay pathaway, autoregulation of the conserved histone H3K9 methyltransferase, and core replication fork-associated proteins in epigenetic maintenance of heterochromatin. In this proposal we will use a combination of in vivo approaches and biochemical assays to investigate (1) the functions of a newly discovered RNA decay complex, called the rixosome, in epigenetic inheritance, (2) the role of a replication fork-associated chromatin assembly complex in retention of histones and epigenetic inheritance during DNA replication, and (3) the role of a conserved ubiquitin ligase in regulation of H3K9 methylation and accurate heterochromatin formation. The ultimate goal of these studies is a molecular understanding of the mechanisms that epigenetically maintain silent chromatin domains.


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 = $334,085 )
2025	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	20	12/12/2024	NON-COMPETING CONTINUATION	$334,085
														Subtotal = $334,085

Issue Date FY: 2024 ( Subtotal = $371,205 )
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	001	19	7/15/2024	NON-COMPETING CONTINUATION	$37,120
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	19	11/17/2023	NON-COMPETING CONTINUATION	$334,085
														Subtotal = $371,205

Issue Date FY: 2023 ( Subtotal = $371,205 )
2023	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	18	12/6/2022	NON-COMPETING CONTINUATION	$334,085
2023	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	001	18	2/14/2023	NON-COMPETING CONTINUATION	$37,120
														Subtotal = $371,205

Issue Date FY: 2022 ( Subtotal = $370,658 )
2022	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	001	17	12/22/2021	COMPETING CONTINUATION	$370,658
2022	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	003	17	7/27/2022	COMPETING CONTINUATION	$0
2022	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	002	16	7/27/2022	NON-COMPETING CONTINUATION	$0
2022	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	16	12/14/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $370,658

Issue Date FY: 2020 ( Subtotal = $360,154 )
2020	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	16	6/10/2020	NON-COMPETING CONTINUATION	$360,154
														Subtotal = $360,154

Issue Date FY: 2019 ( Subtotal = $360,154 )
2019	2019	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	15	6/18/2019	NON-COMPETING CONTINUATION	$360,154
														Subtotal = $360,154

Issue Date FY: 2018 ( Subtotal = $360,154 )
2018	2018	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	001	14	6/20/2018	NON-COMPETING CONTINUATION	$360,154
2018	2016	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	12	12/2/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $360,154

Issue Date FY: 2017 ( Subtotal = $360,154 )
2017	2017	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	003	13	7/21/2017	COMPETING CONTINUATION	$360,154
2017	2016	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	002	12	7/18/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
2017	2016	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	001	12	11/29/2016	EXTENSION WITH OR WITHOUT FUNDS	$59,540
2017	2015	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	11	11/29/2016	NON-COMPETING CONTINUATION	-$59,540
														Subtotal = $360,154

Issue Date FY: 2016 ( Subtotal = $351,713 )
2016	2016	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	12	4/29/2016	EXTENSION WITH OR WITHOUT FUNDS	$351,713
														Subtotal = $351,713

Issue Date FY: 2015 ( Subtotal = $351,713 )
2015	2015	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	11	4/13/2015	NON-COMPETING CONTINUATION	$351,713
														Subtotal = $351,713

Issue Date FY: 2014 ( Subtotal = $351,713 )
2014	2014	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	10	4/8/2014	NON-COMPETING CONTINUATION	$351,713
														Subtotal = $351,713

Issue Date FY: 2013 ( Subtotal = $351,713 )
2013	2013	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	9	7/19/2013	COMPETING CONTINUATION	$351,713
														Subtotal = $351,713

Issue Date FY: 2012 ( Subtotal = $347,397 )
2012	2012	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	8	1/16/2012	NON-COMPETING CONTINUATION	$312,658
2012	2012	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	001	8	3/9/2012	NON-COMPETING CONTINUATION	$34,739
														Subtotal = $347,397

Issue Date FY: 2011 ( Subtotal = $345,096 )
2011	2011	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	7	2/9/2011	NON-COMPETING CONTINUATION	$323,135
2011	2011	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	001	7	7/25/2011	NON-COMPETING CONTINUATION	$21,961
														Subtotal = $345,096

Issue Date FY: 2010 ( Subtotal = $337,212 )
2010	2010	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	6	1/25/2010	NON-COMPETING CONTINUATION	$337,212
														Subtotal = $337,212

Issue Date FY: 2009 ( Subtotal = $358,741 )
2009	2009	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	001	5	1/28/2009	COMPETING CONTINUATION	$358,741
2009	2008	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	4	1/28/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $358,741

Issue Date FY: 2008 ( Subtotal = $280,719 )
2008	2008	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	4	2/15/2008	NON-COMPETING CONTINUATION	$280,719
														Subtotal = $280,719

Issue Date FY: 2007 ( Subtotal = $280,719 )
2007	2007	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	3	1/25/2007	NON-COMPETING CONTINUATION	$280,719
														Subtotal = $280,719

Issue Date FY: 2006 ( Subtotal = $310,423 )
2006	2006	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	2	1/23/2006	NON-COMPETING CONTINUATION	$310,423
														Subtotal = $310,423

Grand Total All Awards = $6,872,822

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Epigenetic inheritance of heterochromatin

Award Number: R01GM072805

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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