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Mechanisms Underlying Enhancer Rnp Mediated Gene Regulation And Genome Organization

Award Number: R01GM136922
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: 09/10/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Mechanisms Underlying Enhancer Rnp Mediated Gene Regulation And Genome Organization - PROJECT ABSTRACT Enhancers play critical roles in determining lineage-specific gene expression and cellular identities, and are enriched in noncoding disease mutations and risk loci. There is an urgent need to elucidate the complete mechanisms of enhancer functions and malfunctions to better understand disease etiology and to develop new, enhancer-targeting therapies. The recent finding that active enhancers often generate noncoding enhancer RNAs (eRNAs) has provided a new perspective to interpret enhancer activity in the context of RNA-mediated regulation. This proposal aims to establish a unique research direction by developing new approaches to address the molecular mechanisms underlying eRNA functions in gene/genome regulation. Our overall hypothesis is that eRNAs assemble specific ribonucleoprotein complexes (RNPs) to organize high-order enhancer structures in the three-dimensional nucleus to control gene transcription. We have three specific aims in this proposal. We plan to use a robust RNA capture method that we have developed to systematically identify eRNA:protein interactomes in human cells. For the first aim, we plan to focus on two novel eRNA- binding proteins (eRBPs) to characterize their functions in gene transcription and 3D genome interaction in mammalian cells. Subsequently, we have two aims to study the mechanisms of each of the two eRBPs to fully characterize the biochemical basis permitting eRNA:protein interaction and their possible involvement in mediating the formation of transcriptionally-associated sub-nuclear condensates. The expected results from this proposal will provide novel mechanistic insights into gene transcriptional regulation and RNA functions in mammalian cells. As enhancers become important drivers in disease development, these mechanistic insights may offer new therapeutic strategies to treat enhancer-driven diseases.


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: 2024 ( Subtotal = $357,741 )
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	5	8/23/2024	NON-COMPETING CONTINUATION	$357,741
														Subtotal = $357,741

Issue Date FY: 2023 ( Subtotal = $357,741 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	4	8/4/2023	NON-COMPETING CONTINUATION	$357,741
														Subtotal = $357,741

Issue Date FY: 2022 ( Subtotal = $357,741 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	3	8/19/2022	NON-COMPETING CONTINUATION	$357,741
														Subtotal = $357,741

Issue Date FY: 2021 ( Subtotal = $552,631 )
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	001	2	9/3/2021	SUPPLEMENT FOR EXPANSION	$194,890
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	2	8/3/2021	NON-COMPETING CONTINUATION	$357,741
														Subtotal = $552,631

Issue Date FY: 2020 ( Subtotal = $357,741 )
2020	2020	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	1	9/10/2020	NEW	$357,741
														Subtotal = $357,741

Grand Total All Awards = $1,983,595

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Mechanisms Underlying Enhancer Rnp Mediated Gene Regulation And Genome Organization

Award Number: R01GM136922

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: 09/10/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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