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A new paradigm of general transcription factor TFIIB functionality in termination and promoter directionality

Award Number: R01GM146803
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: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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A new paradigm of general transcription factor TFIIB functionality in termination and promoter directionality - Project Summary Regulated transcription of genes is essential for cell proliferation, differentiation and viability. Any misregulation may lead to a disease or a developmental abnormality. The transcription cycle of eukaryotic genes consists of multiple steps. The accomplishment of each of these steps requires a number of accessory factors. The initiation of transcription by RNAPII requires gene-specific factors and the general transcription factors (GTFs). The conventional view is that the general transcription factors (GTFs) operate exclusively at the initiation step of transcription. Many recent studies have challenged this dogma. The successful execution of the transcription cycle requires some GTFs to function at the termination step as well. Evidence from my laboratory and others has demonstrated that the general transcription factor TFIIB has an evolutionarily conserved role in termination of transcription. My laboratory has further implicated TFIIB in promoter directionality. Our preliminary results strongly suggest that the mechanistic basis of TFIIB action is, in both cases, dependent on its ability to interact with the termination factors and facilitate their recruitment on the gene. An investigation into the role of TFIIB in termination and directionality is critical to understanding of transcriptional regulation in eukaryotes, and may provide clues into the role TFIIB plays in several diseases. The overall objective of this application is to determine the prevalence and the molecular basis underlying termination of transcription and promoter directionality by TFIIB. The central hypothesis of this application is that TFIIB is involved in termination and promoter directionality of at least a subset of genes. We propose that these apparently unrelated processes rely on the ability of TFIIB to recruit termination factors. To accomplish the objectives of the proposal, we propose the following Specific Aims: (1) Genomewide analysis of TFIIB functions in termination and promoter directionality; (2) Elucidate the molecular basis underlying role of TFIIB in termination and promoter directionality; (3) Purification and characterization of the holo-TFIIB complex. The successful completion of this proposal will enable us to comprehend the role of transcription factors in the broader context, and will serve as a paradigm for understanding the coordination among steps of the transcription cycle in yeast and mammalian systems.


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 = $307,648 )
2025	2025	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Biomedical Research and Research Training	000	4	5/19/2025	NON-COMPETING CONTINUATION	$307,648
														Subtotal = $307,648

Issue Date FY: 2024 ( Subtotal = $343,152 )
2024	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Biomedical Research and Research Training	001	3	8/26/2024	SUPPLEMENT FOR EXPANSION	$41,849
2024	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Biomedical Research and Research Training	000	3	5/9/2024	NON-COMPETING CONTINUATION	$301,303
														Subtotal = $343,152

Issue Date FY: 2023 ( Subtotal = $304,016 )
2023	2023	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Biomedical Research and Research Training	000	2	5/16/2023	NON-COMPETING CONTINUATION	$304,016
														Subtotal = $304,016

Issue Date FY: 2022 ( Subtotal = $303,542 )
2022	2022	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Biomedical Research and Research Training	000	1	8/29/2022	NEW	$303,542
														Subtotal = $303,542

Grand Total All Awards = $1,258,358

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A new paradigm of general transcription factor TFIIB functionality in termination and promoter directionality

Award Number: R01GM146803

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: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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