Thursday, October 17, 2024 10/17/2024

Tissue biology studies of histone modification, nascent transcription, and post-transcription regulation

Award Number: R01AR073806
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract Basic cellular processes essential to mammalian tissue development and adult regeneration, are often controlled by gene expression regulation at the mRNA level. Total mRNA level for each gene depends on two mechanisms: active (or ‘nascent’) transcription and post-transcriptional RNA stability/degradation (e.g. turnover rates). Nascent transcription itself is regulated by multiple steps of recruiting histone-modifying enzymes and opening chromatin, RNA polymerase II (Pol II) initiation and pausing, and the release of Pol II into productive RNA elongation. Diverse mechanisms that regulate total mRNA level may be important in controlling distinct biological processes and pathologies, but this is poorly understood in vivo. Using skin as a model system we will map lineage-specific gene patterns of RNA Pol II activity and nascent transcription in specific cell-types within their natural tissue milieu in the absence of cell isolation. Furthermore, we will investigate changes in these nascent-transcription patterns along an adult tissue stem cell activation and differentiation path, using hair follicle as a lineage prototype. In addition, our work will help dissect relative contributions of active transcription vs post-transcriptional RNA turnover/stability to overall mRNA levels in specific cell types in vivo. Furthermore, we will determine how a known histone repressive mark (H3K9me3), poorly understood in mammalian tissues, acts on nascent transcription and RNA Pol II pausing in vivo. We will uncover for the first time the physiological role of the 3 main H3K9me3 histone methyl transferases in skin development and homeostasis. Finally, we will investigate how H3K9me3 acts on nascent transcription in vivo using our newly developed mouse genetics tools and methodologies. Our work will provide previously unavailable mechanistic insight into gene regulation in mammalian tissue biology using skin as a model system.


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 = $553,544 )
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	7	7/10/2024	NON-COMPETING CONTINUATION	$553,544
2024	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	6	6/4/2024	COMPETING CONTINUATION	$43,787
2024	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	6/4/2024	NON-COMPETING CONTINUATION	-$43,787
														Subtotal = $553,544

Issue Date FY: 2023 ( Subtotal = $570,665 )
2023	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	6	7/26/2023	COMPETING CONTINUATION	$570,665
2023	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	7/11/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $570,665

Issue Date FY: 2022 ( Subtotal = $348,892 )
2022	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	4/29/2022	NON-COMPETING CONTINUATION	$348,892
														Subtotal = $348,892

Issue Date FY: 2021 ( Subtotal = $342,066 )
2021	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	4/16/2021	NON-COMPETING CONTINUATION	$342,066
														Subtotal = $342,066

Issue Date FY: 2020 ( Subtotal = $352,855 )
2020	2020	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	4/6/2020	NON-COMPETING CONTINUATION	$352,855
														Subtotal = $352,855

Issue Date FY: 2019 ( Subtotal = $353,044 )
2019	2019	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	3/29/2019	NON-COMPETING CONTINUATION	$353,044
														Subtotal = $353,044

Issue Date FY: 2018 ( Subtotal = $353,217 )
2018	2018	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	6/29/2018	NEW	$353,217
														Subtotal = $353,217

Grand Total All Awards = $2,874,283

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Tissue biology studies of histone modification, nascent transcription, and post-transcription regulation

Award Number: R01AR073806

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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