Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Mechanisms of Transcriptional Control Revealed by Nascent Transcript Sequencing

Award Number: R01HG007173
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2013
PERIOD OF PERFORMANCE END DATE: 01/31/2027

Group Awards By:

View Award Description

Mechanisms of Transcriptional Control Revealed by Nascent Transcript Sequencing - Transcription initiation is highly regulated by genomic elements in promoters and enhancers that bind transcription factors and recruit RNA polymerase II (Pol II). After Pol II escapes from the promoter, many regulatory steps occur during transcription elongation that control Pol II progression, RNA processing, and finally release of the RNA from chromatin for nuclear export. These steps are tightly controlled by genomic and epigenomic features, such as histone modifications, nucleosome positions, and cis-elements that bind transcription factors and RNA-binding proteins (RBPs). Current functional genomic technologies tend to provide a static, averaged view of genomic function that obscure the transient roles that many genomic elements play in shaping the transcriptome. To identify and characterize all functional genomic elements, we need to develop approaches that quantitatively monitor the many layers of gene expression regulation, including transient interactions and short-lived events. In the proposed research, we will create a suite of genome-wide tools to map Pol II across single chromatin fibers, track the association of RBPs, and follow RNAs from transcription initiation to nuclear export. These techniques will highlight unappreciated connections between genomic elements, molecular events on chromatin, and post-initiation regulatory events. Our rationale is that by creating tools to quantify short-lived steps in mRNA production, unappreciated functional roles for genomic elements can be revealed. To demonstrate how these technologies reveal unappreciated gene regulatory mechanisms, we will apply them to the heat shock response (HSR), a stress response that has served as a model to study the many regulatory layers in gene expression. In Aim 1 we will develop a strategy that reveals Pol II locations across single long chromatin fibers. Fiber-seq is a method that identifies regions of accessible DNA across long (up to ~20 kb) chromatin fibers one molecule at a time. We will extend this approach to identify Pol II footprints, analyze the distributions of Pol II complexes across gene bodies, and characterize the interactions between Pol II complexes and nucleosomes. In Aim 2 we will measure the timing of binding of proteins across long pre-mRNA molecules. RBP binding will be marked by RNA editing and long- read direct RNA sequencing of nascent RNA (nano-COP) will enable us to resolve transient binding events that impact pre-mRNA processing and nuclear export. These events are transient, as many RBPs bind to introns and are released from RNA in the cytoplasm immediately after nuclear export. In Aim 3, we will create an approach to measure kinetics of RNA production, chromatin release, and nuclear export that couples 4sU metabolic labeling of newly synthesized RNAs with biochemical purification of RNAs from chromatin, nucleoplasm, and cytoplasm. The data from this technique will allow us to estimate the rates of release of RNA from chromatin, nuclear export of RNA, and cytoplasmic degradation of every RNA. Using public datasets from ENCODE and elsewhere, we will identify and test hypotheses for the determinants of RNA lifetimes.


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 = $580,405 )
2026	2026	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	000	13	3/2/2026	NON-COMPETING CONTINUATION	$580,405
														Subtotal = $580,405

Issue Date FY: 2025 ( Subtotal = $580,405 )
2025	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	000	12	1/23/2025	NON-COMPETING CONTINUATION	$580,405
2025	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	001	12	4/21/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $580,405

Issue Date FY: 2024 ( Subtotal = $580,405 )
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	002	11	1/18/2024	NON-COMPETING CONTINUATION	$533,024
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	003	11	7/26/2024	NON-COMPETING CONTINUATION	$47,381
2024	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	001	10	1/17/2024	COMPETING CONTINUATION	$676
2024	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	000	9	1/17/2024	NON-COMPETING CONTINUATION	-$676
														Subtotal = $580,405

Issue Date FY: 2023 ( Subtotal = $592,249 )
2023	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	001	10	1/27/2023	COMPETING CONTINUATION	$526,444
2023	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	002	10	3/2/2023	COMPETING CONTINUATION	$65,805
2023	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	000	9	1/27/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $592,249

Issue Date FY: 2021 ( Subtotal = $513,500 )
2021	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	000	9	5/24/2021	NON-COMPETING CONTINUATION	$513,500
														Subtotal = $513,500

Issue Date FY: 2020 ( Subtotal = $517,318 )
2020	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	000	8	5/26/2020	NON-COMPETING CONTINUATION	$517,318
														Subtotal = $517,318

Issue Date FY: 2019 ( Subtotal = $513,500 )
2019	2019	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	002	7	5/20/2019	NON-COMPETING CONTINUATION	$513,500
2019	2018	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	001	6	11/29/2018	COMPETING CONTINUATION	$72,008
2019	2017	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	000	5	11/29/2018	NON-COMPETING CONTINUATION	-$72,008
														Subtotal = $513,500

Issue Date FY: 2018 ( Subtotal = $592,501 )
2018	2018	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	001	6	8/10/2018	COMPETING CONTINUATION	$592,501
2018	2017	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	000	5	8/9/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $592,501

Issue Date FY: 2017 ( Subtotal = $423,750 )
2017	2017	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	001	5	7/21/2017	NON-COMPETING CONTINUATION	$42,375
2017	2017	HARVARD COLLEGE, PRESIDENT & FELLOWS OF	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	000	5	3/15/2017	NON-COMPETING CONTINUATION	$381,375
														Subtotal = $423,750

Issue Date FY: 2016 ( Subtotal = $519,704 )
2016	2016	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	000	4	4/7/2016	EXTENSION WITH OR WITHOUT FUNDS	$519,704
														Subtotal = $519,704

Issue Date FY: 2015 ( Subtotal = $493,740 )
2015	2015	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	000	3	4/9/2015	NON-COMPETING CONTINUATION	$413,156
2015	2015	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	001	3	7/7/2015	SUPPLEMENT FOR EXPANSION	$80,584
														Subtotal = $493,740

Issue Date FY: 2014 ( Subtotal = $415,275 )
2014	2014	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	000	2	3/13/2014	NON-COMPETING CONTINUATION	$415,275
														Subtotal = $415,275

Issue Date FY: 2013 ( Subtotal = $423,438 )
2013	2013	HARVARD UNIVERSITY MEDICAL SCHOOL	643 HUNTINGTON AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Human Genome Research	000	1	3/26/2013	NEW	$423,438
														Subtotal = $423,438

Grand Total All Awards = $6,746,190

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanisms of Transcriptional Control Revealed by Nascent Transcript Sequencing

Award Number: R01HG007173

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2013

PERIOD OF PERFORMANCE END DATE: 01/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer