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Repression of hTERT gene during cell differentiation

Award Number: R01GM071725
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: 08/01/2004
PERIOD OF PERFORMANCE END DATE: 06/30/2022

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Repression of hTERT gene during cell differentiation - Abstract Our long-term goal is to determine the mechanisms of telomerase regulation during development. The hTERT gene, encoding the limiting subunit of human telomerase, is primarily regulated at the level of transcription. It is highly expressed in pluripotent stem cells, but stringently repressed in most somatic cells. Regulation of transcription during development and differentiation often involves distal elements and chromatin reorganization, in addition to proximal promoter elements. We previously showed that the endogenous hTERT locus was embedded in a condensed chromatin domain in many somatic cells. Consistent with the vital role of chromatin in its tight regulation, we found that an episomal hTERT locus in human fibroblasts was not subjected to repression, whereas a chromosomally integrated hTERT locus recapitulated its native regulation. To study the mechanisms of hTERT repression, we developed a novel technical platform, the recombinase-mediated BAC targeting or RMBT method, for targeted integration of single-copy BAC reporters into specified chromosomal sites. This technique enables us to study the regulation of hTERT gene in its native genomic context. Here, we hypothesize that 1) the interplay between distal elements and core promoter in their native chromatin contexts is important for hTERT repression in somatic cells and reactivation in cancer cells; and 2) polymorphic regulatory elements of the hTERT gene impact human aging and tumorigenesis. We propose three specific aims: 1) determine the recruitment of corepressor complexes and their roles in hTERT repression; 2) determine the regulation of hTERT promoter by Ets family proteins in normal and cancer cells; 3) determine the function and genetic variation of a polymorphic element in hTERT regulation and human longevity.


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: 2023 ( Subtotal = -$46,269 )
2023	2020	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Biomedical Research and Research Training	000	14	1/5/2023	NON-COMPETING CONTINUATION	-$46,269
														Subtotal = -$46,269

Issue Date FY: 2020 ( Subtotal = $328,116 )
2020	2020	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Biomedical Research and Research Training	000	14	6/25/2020	NON-COMPETING CONTINUATION	$328,116
														Subtotal = $328,116

Issue Date FY: 2019 ( Subtotal = $478,116 )
2019	2019	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Biomedical Research and Research Training	001	13	7/25/2019	SUPPLEMENT FOR EXPANSION	$150,000
2019	2019	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Biomedical Research and Research Training	000	13	6/20/2019	NON-COMPETING CONTINUATION	$328,116
														Subtotal = $478,116

Issue Date FY: 2018 ( Subtotal = $374,385 )
2018	2018	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Biomedical Research and Research Training	001	12	6/27/2018	NON-COMPETING CONTINUATION	$328,116
2018	2017	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Biomedical Research and Research Training	000	11	11/6/2017	COMPETING CONTINUATION	$46,269
														Subtotal = $374,385

Issue Date FY: 2017 ( Subtotal = $290,333 )
2017	2017	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Biomedical Research and Research Training	001	11	9/13/2017	COMPETING CONTINUATION	$336,602
2017	2013	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Biomedical Research and Research Training	000	10	1/5/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$46,269
														Subtotal = $290,333

Issue Date FY: 2015 ( Subtotal = $0 )
2015	2013	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Biomedical Research and Research Training	000	10	8/25/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = -$3,298 )
2014	2013	MILTON S HERSHEY MEDICAL CENTER	500 UNIVERSITY DRIVE, POB 850	HERSHEY	PA	17033	DAUPHIN	USA	Biomedical Research and Research Training	000	9	5/26/2014	NON-COMPETING CONTINUATION	-$252,200
2014	2013	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Biomedical Research and Research Training	001	10	5/27/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$248,902
														Subtotal = -$3,298

Issue Date FY: 2013 ( Subtotal = $359,389 )
2013	2013	MILTON S HERSHEY MEDICAL CENTER	500 UNIVERSITY DRIVE, POB 850	HERSHEY	PA	17033	DAUPHIN	USA	Biomedical Research and Research Training	000	9	8/22/2013	NON-COMPETING CONTINUATION	$359,389
														Subtotal = $359,389

Issue Date FY: 2012 ( Subtotal = $373,231 )
2012	2012	MILTON S HERSHEY MEDICAL CENTER	500 UNIVERSITY DRIVE, POB 850	HERSHEY	PA	17033	DAUPHIN	USA	Biomedical Research and Research Training	001	8	8/27/2012	SUPPLEMENT FOR EXPANSION	$59,673
2012	2012	MILTON S HERSHEY MEDICAL CENTER	500 UNIVERSITY DRIVE, POB 850	HERSHEY	PA	17033	DAUPHIN	USA	Biomedical Research and Research Training	000	8	8/20/2012	NON-COMPETING CONTINUATION	$313,558
														Subtotal = $373,231

Issue Date FY: 2011 ( Subtotal = $313,558 )
2011	2011	MILTON S HERSHEY MEDICAL CENTER	500 UNIVERSITY DRIVE, POB 850	HERSHEY	PA	17033	DAUPHIN	USA	Biomedical Research and Research Training	000	7	8/24/2011	NON-COMPETING CONTINUATION	$313,558
														Subtotal = $313,558

Issue Date FY: 2010 ( Subtotal = $316,725 )
2010	2010	MILTON S HERSHEY MEDICAL CENTER	500 UNIVERSITY DRIVE, POB 850	HERSHEY	PA	17033	DAUPHIN	USA	Biomedical Research and Research Training	000	6	9/20/2010	COMPETING CONTINUATION	$316,725
														Subtotal = $316,725

Issue Date FY: 2008 ( Subtotal = $361,643 )
2008	2008	MILTON S HERSHEY MEDICAL CENTER	500 UNIVERSITY DRIVE, POB 850	HERSHEY	PA	17033	DAUPHIN	USA	Biomedical Research and Research Training	000	5	7/11/2008	NON-COMPETING CONTINUATION	$246,005
2008	2008	MILTON S HERSHEY MEDICAL CENTER	500 UNIVERSITY DRIVE, POB 850	HERSHEY	PA	17033	DAUPHIN	USA	Biomedical Research and Research Training	001	5	7/31/2008	SUPPLEMENT FOR EXPANSION	$115,638
														Subtotal = $361,643

Issue Date FY: 2007 ( Subtotal = $246,005 )
2007	2007	MILTON S HERSHEY MEDICAL CENTER	500 UNIVERSITY DRIVE, POB 850	HERSHEY	PA	17033	DAUPHIN	USA	Biomedical Research and Research Training	000	4	7/26/2007	NON-COMPETING CONTINUATION	$246,005
														Subtotal = $246,005

Issue Date FY: 2006 ( Subtotal = $253,381 )
2006	2006	MILTON S HERSHEY MEDICAL CENTER	500 UNIVERSITY DRIVE, POB 850	HERSHEY	PA	17033	DAUPHIN	USA	Biomedical Research and Research Training	000	3	7/31/2006	NON-COMPETING CONTINUATION	$253,381
														Subtotal = $253,381

Issue Date FY: 2005 ( Subtotal = $259,507 )
2005	2005	MILTON S HERSHEY MEDICAL CENTER	500 UNIVERSITY DRIVE, POB 850	HERSHEY	PA	17033	DAUPHIN	USA	Biomedical Research and Research Training	000	2	7/22/2005	NON-COMPETING CONTINUATION	$259,507
														Subtotal = $259,507

Issue Date FY: 2004 ( Subtotal = $260,794 )
2004	2004	MILTON S HERSHEY MEDICAL CENTER	500 UNIVERSITY DRIVE, POB 850	HERSHEY	PA	17033	DAUPHIN	USA	Biomedical Research and Research Training	001	1	8/9/2004	SUPPLEMENT FOR EXPANSION	$6,750
2004	2004	MILTON S HERSHEY MEDICAL CENTER	500 UNIVERSITY DRIVE, POB 850	HERSHEY	PA	17033	DAUPHIN	USA	Biomedical Research and Research Training	000	1	7/1/2004	NEW	$254,044
														Subtotal = $260,794

Grand Total All Awards = $4,165,616

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Repression of hTERT gene during cell differentiation

Award Number: R01GM071725

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: 08/01/2004

PERIOD OF PERFORMANCE END DATE: 06/30/2022

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