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Structural Annotation of the Human Genome

Award Number: R01HG003143
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2003
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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View Award Description

Structural Annotation of the Human Genome - PROJECT SUMMARY Cells must regulate their genome so that genes are expressed in the appropriate cell type, and at the correct time. Further, as cells go through the cell cycle chromosomes must be replicated, compacted and then faithfully segregated. All these processes require correct folding of the genome. Defects in folding, e.g., the looping of genes to incorrect distal enhancers, or incorrect chromosome compaction during mitosis, can lead to genes being expressed in the wrong place and at the wrong time, or to genome instability. Such defects can lead to diseases including cancer. There has been tremendous progress in identifying folding principles of chromosomes, how folding changes during the cell cycle, roles of cis elements in folding chromosomes and long-range gene regulation, and the molecular machines and mechanisms that fold chromosomes. In interphase chromosomes fold into topologically associating domains and cohesin-mediated loops. Chromosomes also compartmentalize to form active and inactive chromatin domains through a phase separation process. In mitosis, chromosomes refold into linearly compressed arrays of condensin-mediated loops. We and others showed that alternation of cohesin-mediated loop formation and condensin-mediated loop formation drives cell cycle stage-dependent chromosome folding. However, three critical aspects of chromosome organization have remained largely unexplored, mostly due to lack of experimental approaches. First, little is known about the identity of cis elements that mediate interactions between sister chromatids, yet these interactions are critical for faithful chromosome segregation. Second, the topological state of chromosomes, i.e., the presence of intra- and inter-chromosomal catenations is almost entirely unexplored. Catenations form during replication and transcription and these create impediments to correct gene expression and chromosome segregation and therefore the cell must constantly resolve these. Cis elements and trans factors involved in controlling the topological state of the genome are largely uncharacterized. Third, factors and cis elements driving chromosome compartmentalization are poorly characterized. We recently developed three new genomic technologies, SisterC, Multi-Contact 3C, and Liquid Chromatin Hi-C that allow studying each of these three outstanding questions respectively. Here, we will employ these methods to identify genomic DNA elements, and their mode of action, that control chromosome compartmentalization, catenation and decatenation, and that play roles in disentangling and segregating sister chromatids.


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: 2026 ( Subtotal = $731,771 )
2026	2026	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Human Genome Research	000	21	4/9/2026	NON-COMPETING CONTINUATION	$731,771
														Subtotal = $731,771

Issue Date FY: 2025 ( Subtotal = $658,597 )
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Human Genome Research	000	20	4/2/2025	NON-COMPETING CONTINUATION	$658,597
														Subtotal = $658,597

Issue Date FY: 2024 ( Subtotal = $731,774 )
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Human Genome Research	002	19	7/26/2024	NON-COMPETING CONTINUATION	$59,736
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Human Genome Research	001	19	3/12/2024	NON-COMPETING CONTINUATION	$672,038
2024	2021	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Human Genome Research	000	17	2/1/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $731,774

Issue Date FY: 2023 ( Subtotal = $757,927 )
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Human Genome Research	000	18	5/19/2023	COMPETING CONTINUATION	$757,927
														Subtotal = $757,927

Issue Date FY: 2021 ( Subtotal = $748,392 )
2021	2021	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Human Genome Research	000	17	5/12/2021	NON-COMPETING CONTINUATION	$748,392
														Subtotal = $748,392

Issue Date FY: 2020 ( Subtotal = $748,392 )
2020	2020	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Human Genome Research	000	16	5/13/2020	NON-COMPETING CONTINUATION	$748,392
														Subtotal = $748,392

Issue Date FY: 2019 ( Subtotal = $761,567 )
2019	2019	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Human Genome Research	001	15	5/23/2019	NON-COMPETING CONTINUATION	$761,567
2019	2017	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Human Genome Research	000	13	11/29/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $761,567

Issue Date FY: 2018 ( Subtotal = $778,442 )
2018	2018	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Human Genome Research	001	14	7/25/2018	COMPETING CONTINUATION	$778,442
2018	2017	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Human Genome Research	000	13	7/24/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $778,442

Issue Date FY: 2017 ( Subtotal = $815,222 )
2017	2017	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Human Genome Research	000	13	7/7/2017	NON-COMPETING CONTINUATION	$815,222
														Subtotal = $815,222

Issue Date FY: 2016 ( Subtotal = $815,922 )
2016	2016	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Human Genome Research	000	12	7/6/2016	NON-COMPETING CONTINUATION	$815,922
														Subtotal = $815,922

Issue Date FY: 2015 ( Subtotal = $796,175 )
2015	2015	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Human Genome Research	000	11	6/30/2015	NON-COMPETING CONTINUATION	$796,175
														Subtotal = $796,175

Issue Date FY: 2014 ( Subtotal = $834,099 )
2014	2014	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Human Genome Research	001	10	6/30/2014	COMPETING CONTINUATION	$834,099
2014	2013	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Human Genome Research	000	9	6/25/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $834,099

Issue Date FY: 2013 ( Subtotal = $734,468 )
2013	2013	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Human Genome Research	000	9	6/5/2013	NON-COMPETING CONTINUATION	$734,468
														Subtotal = $734,468

Issue Date FY: 2012 ( Subtotal = $793,500 )
2012	2012	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Human Genome Research	000	8	5/10/2012	NON-COMPETING CONTINUATION	$793,500
														Subtotal = $793,500

Issue Date FY: 2011 ( Subtotal = $800,066 )
2011	2011	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Human Genome Research	004	7	8/21/2011	COMPETING CONTINUATION	$800,066
2011	2010	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Human Genome Research	001	6	3/21/2011	SUPPLEMENT FOR EXPANSION	$0
2011	2010	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Human Genome Research	003	6	8/18/2011	SUPPLEMENT FOR EXPANSION	$0
2011	2009	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Human Genome Research	002	6	8/18/2011	NON-COMPETING CONTINUATION	$0
2011	2009	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Human Genome Research	000	6	3/21/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $800,066

Issue Date FY: 2010 ( Subtotal = $555,000 )
2010	2010	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Human Genome Research	000	6	8/28/2010	SUPPLEMENT FOR EXPANSION	$555,000
														Subtotal = $555,000

Issue Date FY: 2009 ( Subtotal = $1,066,715 )
2009	2009	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Trans-NIH Recovery Act Research Support	001	6	9/11/2009	SUPPLEMENT FOR EXPANSION	$512,696
2009	2009	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Human Genome Research	000	6	3/23/2009	NON-COMPETING CONTINUATION	$554,019
														Subtotal = $1,066,715

Issue Date FY: 2008 ( Subtotal = $540,829 )
2008	2008	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Human Genome Research	000	5	4/18/2008	NON-COMPETING CONTINUATION	$540,829
														Subtotal = $540,829

Issue Date FY: 2007 ( Subtotal = $582,000 )
2007	2007	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Human Genome Research	000	4	3/30/2007	COMPETING CONTINUATION	$582,000
														Subtotal = $582,000

Issue Date FY: 2005 ( Subtotal = $397,500 )
2005	2005	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Human Genome Research	000	3	8/31/2005	NON-COMPETING CONTINUATION	$397,500
														Subtotal = $397,500

Grand Total All Awards = $15,400,878

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Structural Annotation of the Human Genome

Award Number: R01HG003143

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2003

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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