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Know your neighbors: investigating the influence of gene co-localization on transcriptional dynamics

Award Number: R15GM132896
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: 08/01/2019
PERIOD OF PERFORMANCE END DATE: 07/31/2023

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Know your neighbors: investigating the influence of gene co-localization on transcriptional dynamics - In the crowded and dynamic three-dimensional space of the nucleus, active genes often share local neighborhoods with one another. Despite significant recent progress in analyses of 3D positioning of genes, it is not yet fully understood how the co-localization of genes plays a role in their transcriptional output. The long-term goal of this research is to understand how a gene’s expression is influenced by its neighbors in space and time. The study of how co-localized genes share local resources has the potential to shed significant light on fundamental mechanisms of transcription, but progress has been severely limited by a reliance on methods that examine transcription and 3D position separately in fixed or disrupted tissues. The objective of this proposal is to uncover the impact of gene co-localization on transcriptional dynamics in living cells to provide a dynamic spatiotemporal quantification of transcription for genes that share a local 3D neighborhood. To address this objective, the proposal focuses on Drosophila melanogaster and takes advantage of a phenomenon called transvection, where sequences at allelic positions on homologous chromosomes are stably co-localized via a process called somatic homolog pairing. Furthermore, the proposed experiments employ the MS2 and PP7 systems for live analysis of transcriptional dynamics, which permit simultaneous quantification of transcriptional activity and assessment of the 3D positions of genes over time in living cells. The central hypothesis guiding the proposal is that co-localization of genes via somatic homolog pairing will result in the sharing of local stores of resources necessary for transcription, which can be understood by analyzing how co-localization influences the parameters of transcriptional dynamics, including the frequency, duration, and amplitudes of transcriptional bursts. This hypothesis is tested in the context of two contrasting scenarios resulting from co-localization of genes via transvection: in one scenario, co-localized promoters in cis and in trans to an enhancer compete for activation, while in a second scenario, co-localized enhancers cooperate to achieve augmented levels of transcriptional output. The proposed experiments have the expected outcome of identifying precisely and quantitatively how interactions between co- localized genes influence transcriptional dynamics, providing key insights into mechanisms by which 3D genome organization controls gene expression.


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 = $0 )
2024	2019	BOWDOIN COLLEGE	255 MAINE ST	BRUNSWICK	ME	04011	CUMBERLAND	USA	Biomedical Research and Research Training	000	1	11/30/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $406,989 )
2019	2019	BOWDOIN COLLEGE	5600 COLLEGE STATION	BRUNSWICK	ME	04011	CUMBERLAND	USA	Biomedical Research and Research Training	000	1	7/22/2019	NEW	$406,989
														Subtotal = $406,989

Grand Total All Awards = $406,989

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Know your neighbors: investigating the influence of gene co-localization on transcriptional dynamics

Award Number: R15GM132896

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: 08/01/2019

PERIOD OF PERFORMANCE END DATE: 07/31/2023

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