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Mechanism of Transcript Elongation in Chromatin by RNA Polymerase II

Award Number: R01GM058650
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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DESCRIPTION (provided by applicant): The vital process of transcription by RNA polymerase II (pol II) occurs in chromatin environment in eukaryotic cells; in fact, moderately transcribed genes retain nucleosomal structure. Recent studies suggest that chromatin structure presents a strong barrier for transcribing pol II in vitro, and that DNA-histone interactions are only partialy and transiently disrupted during transcript elongation on moderately active genes. Furthermore, elongating pol II complex is one of the major targets during gene regulation. The nucleosomal barrier and protein factors interacting with histones and pol II participate in this regulation. These studies raise the following questions: (1) How do eukaryotic polymerases overcome the nucleosome barrier? (2) What are the mechanisms of histone recovery during progression of pol II through chromatin? (3) How do the factors interacting with chromatin and with the target enzymes change the rate of pol II progression through chromatin? The long-term research goal of this proposal is to understand the mechanism and the regulation of transcript elongation by pol II in chromatin. The specific questions will be addressed in a highly purified transcription system in vitro. We will analyze transcription of homogeneous and well-defined mono- and polynucleosomal chromatin templates using a combination of biochemical, fluorescent, molecular genetic and single-molecule techniques. Our experiments will be focused on analysis of eukaryotic pol II. Our preliminary studies have shown that transcription through chromatin is accompanied by transient DNA uncoiling from histones and unfolding of histone octamer. The structures of these intermediates and the rates of interconversion between them largely determine the outcome of the process of transcription through chromatin. Accordingly, the specific aims are: 1. To provide molecular description of the changes in DNA-histone interactions during transcription through chromatin by pol II and the rates of interconversion between the intermediates. 2. To identify protein-protein interactions perturbed during transcription-dependent unfolding of the histone octamer, and factors involved in this process. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page


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: 2017 ( Subtotal = $0 )
2017	2015	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	000	18	6/5/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $365,925 )
2015	2015	INSTITUTE FOR CANCER RESEARCH	333 Cottman Ave	Philadelphia	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	000	18	1/29/2015	NON-COMPETING CONTINUATION	$365,925
														Subtotal = $365,925

Issue Date FY: 2014 ( Subtotal = $363,283 )
2014	2014	INSTITUTE FOR CANCER RESEARCH	333 Cottman Ave	Philadelphia	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	002	17	4/4/2014	NON-COMPETING CONTINUATION	$365,925
2014	2013	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	001	15	4/1/2014	NON-COMPETING CONTINUATION	$18,309
2014	2013	INSTITUTE FOR CANCER RESEARCH	333 Cottman Ave	Philadelphia	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	000	16	4/1/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$20,951
														Subtotal = $363,283

Issue Date FY: 2013 ( Subtotal = $350,476 )
2013	2013	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	001	15	6/11/2013	NON-COMPETING CONTINUATION	$20,787
2013	2013	INSTITUTE FOR CANCER RESEARCH	333 Cottman Ave	Philadelphia	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	005	16	4/1/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$20,951
2013	2013	INSTITUTE FOR CANCER RESEARCH	333 Cottman Ave	Philadelphia	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	003	16	8/22/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$353,118
2013	2013	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	004	15	4/1/2014	NON-COMPETING CONTINUATION	$18,309
2013	2013	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	002	15	8/21/2013	NON-COMPETING CONTINUATION	-$308,607
2013	2013	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	15	1/18/2013	NON-COMPETING CONTINUATION	$287,820
														Subtotal = $350,476

Issue Date FY: 2012 ( Subtotal = $319,800 )
2012	2012	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	001	14	4/6/2012	COMPETING CONTINUATION	$319,800
2012	2010	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	13	4/6/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $319,800

Issue Date FY: 2010 ( Subtotal = $312,741 )
2010	2010	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	13	4/12/2010	NON-COMPETING CONTINUATION	$312,741
														Subtotal = $312,741

Issue Date FY: 2009 ( Subtotal = $729,192 )
2009	2009	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Trans-NIH Recovery Act Research Support	001	12	7/16/2009	SUPPLEMENT FOR EXPANSION	$413,292
2009	2009	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	12	4/16/2009	NON-COMPETING CONTINUATION	$315,900
														Subtotal = $729,192

Issue Date FY: 2008 ( Subtotal = $315,900 )
2008	2008	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	11	4/4/2008	NON-COMPETING CONTINUATION	$315,900
														Subtotal = $315,900

Issue Date FY: 2007 ( Subtotal = $315,900 )
2007	2007	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	10	7/16/2007	COMPETING CONTINUATION	$315,900
														Subtotal = $315,900

Issue Date FY: 2006 ( Subtotal = $262,694 )
2006	2006	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	9	11/25/2005	NON-COMPETING CONTINUATION	$262,694
														Subtotal = $262,694

Issue Date FY: 2005 ( Subtotal = $269,015 )
2005	2005	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	8	12/10/2004	NON-COMPETING CONTINUATION	$269,015
														Subtotal = $269,015

Issue Date FY: 2004 ( Subtotal = $269,015 )
2004	2004	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	7	12/15/2003	NON-COMPETING CONTINUATION	$269,015
														Subtotal = $269,015

Issue Date FY: 2003 ( Subtotal = $298,221 )
2003	2003	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Genetics and Developmental Biology Research and Research Training	000	6	8/28/2003	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$178,581
2003	2003	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Genetics and Developmental Biology Research and Research Training	000	5		COMPETING CONTINUATION	$119,640
														Subtotal = $298,221

Issue Date FY: 2002 ( Subtotal = $191,089 )
2002	2002	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Genetics and Developmental Biology Research and Research Training	000	4	11/30/2001	NON-COMPETING CONTINUATION	$191,089
														Subtotal = $191,089

Issue Date FY: 2001 ( Subtotal = $185,610 )
2001	2001	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Genetics and Developmental Biology Research and Research Training	000	3	1/10/2001	NON-COMPETING CONTINUATION	$185,610
														Subtotal = $185,610

Issue Date FY: 2000 ( Subtotal = $180,290 )
2000	2000	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Genetics and Developmental Biology Research and Research Training	000	2	12/17/1999	NON-COMPETING CONTINUATION	$180,290
														Subtotal = $180,290

Issue Date FY: 1999 ( Subtotal = $218,478 )
1999	1999	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Genetics and Developmental Biology Research and Research Training	000	1	2/26/1999	NEW	$218,478
														Subtotal = $218,478

Grand Total All Awards = $4,947,629

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Mechanism of Transcript Elongation in Chromatin by RNA Polymerase II

Award Number: R01GM058650

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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