Thursday, July 3, 2025 7/3/2025

The effect of nucleosomes on the earliest stages of RNA polymerase II transcription

Award Number: R01GM121428
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: 09/01/2018
PERIOD OF PERFORMANCE END DATE: 05/31/2028

Group Awards By:

View Award Description

The effect of nucleosomes on the earliest stages of RNA polymerase II transcription - Project summary- Much of the control of gene expression is exerted at two points: assembly of the RNA polymerase II (Pol II) preinitiation complex at promoters and the successful advance of Pol II into productive elongation. Pol II promoters are accompanied by an immediately downstream (+1) nucleosome typically located just beyond the likely boundary of the promoter. It is often speculated that promoter activity is controlled by this distinctive local chromatin architecture, which includes histone modifications and histone variants specific to promoter-proximal nucleosomes. However, the roles that adjacent nucleosomes play in the assembly of the transcription complex remain poorly understood. After transcription initiates Pol II complexes elongate very slowly, eventually encountering the +1 nucleosome while associating with positive and negative factors. Most of these complexes terminate while a minority advance into effective elongation and traverse the nucleosome. The extent to which complexes achieve full elongation competence is a major determinant of overall promoter strength, but it is not known how the +1 nucleosome barrier modulates the crucial competition between maturation into productive elongation and termination. Our overall aim is to biochemically dissect Pol II initiation and early elongation to understand the mechanistic basis for distinct outcomes for Pol II complexes within the local chromatin context. We are approaching these questions using a nuclear extract based in vitro transcription system in which transcription complex assembly and early elongation are challenged by a +1 nucleosome positioned at a series of precise downstream locations. These nucleosomes can include the histone modifications and histone variants typically found near promoters. Our current results already provide important and novel insights into both the negative and positive effects of +1 nucleosomes on transcription complex assembly. These effects depend significantly on promoter class (presence or absence of the TATA element) and on promoter-enriched histone modifications whose function is currently unknown. In the studies proposed here, we will substantially extend the present findings to uncover the mechanistic basis for the control of Pol II transcription complex assembly by the +1 nucleosome. We have also found with extract-based transcription that both the advance into productive elongation and termination can be studied in single reactions. This will allow us for the first time to uncover the mechanisms and factors that competitively drive both relevant fates for Pol II immediately following initiation from a promoter in the context of an appropriately located and modified +1 nucleosome.


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 = $373,119 )
2025	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Biomedical Research and Research Training	002	6	5/14/2025	NON-COMPETING CONTINUATION	$373,119
2025	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Biomedical Research and Research Training	001	5	3/24/2025	COMPETING CONTINUATION	$1,806
2025	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Biomedical Research and Research Training	000	4	3/24/2025	NON-COMPETING CONTINUATION	-$1,806
														Subtotal = $373,119

Issue Date FY: 2024 ( Subtotal = $373,119 )
2024	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Biomedical Research and Research Training	001	5	7/10/2024	COMPETING CONTINUATION	$373,119
2024	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Biomedical Research and Research Training	000	4	7/9/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $373,119

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Biomedical Research and Research Training	000	4	7/19/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $223,088 )
2021	2021	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Biomedical Research and Research Training	000	4	8/12/2021	NON-COMPETING CONTINUATION	$223,088
														Subtotal = $223,088

Issue Date FY: 2020 ( Subtotal = $333,966 )
2020	2020	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Biomedical Research and Research Training	000	3	8/11/2020	NON-COMPETING CONTINUATION	$333,966
														Subtotal = $333,966

Issue Date FY: 2019 ( Subtotal = $332,477 )
2019	2019	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Biomedical Research and Research Training	000	2	8/12/2019	NON-COMPETING CONTINUATION	$332,477
														Subtotal = $332,477

Issue Date FY: 2018 ( Subtotal = $347,179 )
2018	2018	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE/CWRU	9500 EUCLID AVE	CLEVELAND	OH	44195	CUYAHOGA	USA	Biomedical Research and Research Training	000	1	8/17/2018	NEW	$347,179
														Subtotal = $347,179

Grand Total All Awards = $1,982,948

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The effect of nucleosomes on the earliest stages of RNA polymerase II transcription

Award Number: R01GM121428

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: 09/01/2018

PERIOD OF PERFORMANCE END DATE: 05/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer