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Mechanisms of condensin-mediated gene regulation in C. elegans

Award Number: R35GM130311
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: 05/31/2029

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Mechanisms of condensin-mediated gene regulation in C. elegans - Research summary Regulation of transcription is essential for cell function. In eukaryotes, diverse mechanisms control transcription through chromatin structure and organization of DNA within the nucleus. Histone modifications modulate the activity of gene regulatory elements and regulate binding of proteins that form transcriptionally active and inactive compartments. Structural maintenance of chromosomes (SMC) complexes bind and translocate on DNA, forming loops that bring distant sites into contact. As the molecular activities of individual chromatin modifiers and SMC complexes are being studied, it is important to determine how they integrate with each other to control transcription during development and differentiation. Our research program addresses the functional interactions between SMC complexes, chromatin, and transcription around three topics. The first focuses on condensin, a eukaryotic SMC complex that has been challenging to study in vivo because it is essential for cell division and binds chromosomes transiently during mitosis. In the nematode Caenorhabditis elegans, a hermaphrodite-specific condensin functions throughout the cell cycle to repress X chromosome transcription for dosage compensation. Condensin DC also controls histone modifications, providing an excellent system to study integration of SMC activity and chromatin modifiers for transcription regulation. The second topic focuses on the interaction between condensin and cohesin, another SMC that regulates the organization of eukaryotic genomes during interphase. As cells progress from interphase to mitosis, cohesin binding and activity decreases while condensin’s increase and transcription is silenced. This transition is key to regulation of cell-type specific transcriptional programs during differentiation. By addressing how condensin DC interacts with cohesin on the X chromosomes, we believe our work can provide insights into the interphase to mitotic transition of the eukaryotic genomes. The third topic is regulation of RNA Polymerase III, which transcribes a diverse array of small functional RNAs, including tRNAs. RNA Pol III regulation is relatively understudied and is important for protein translation in health and disease. Due to unique chromosomal distribution of tRNA genes, our work in C. elegans dosage compensation puts us in an ideal place to study the mechanisms that regulate RNA Pol III transcription. In the next five years our research will provide significant insights into how cohesin, condensin and chromatin work together to regulate transcription during development and differentiation. Our program is also evolving to address environmental gene regulation and RNA Pol III transcription – new and important areas of study to understand basic mechanisms of genome organization and function throughout the life of an organism.


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 = $418,408 )
2026	2026	NEW YORK UNIVERSITY	70 WASHINGTON SQ S FL 11	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	8	5/5/2026	NON-COMPETING CONTINUATION	$418,408
														Subtotal = $418,408

Issue Date FY: 2025 ( Subtotal = $413,105 )
2025	2025	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	002	7	4/29/2025	NON-COMPETING CONTINUATION	$413,105
2025	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	6	11/11/2024	COMPETING CONTINUATION	$0
2025	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S FL 11	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	001	5	2/18/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $413,105

Issue Date FY: 2024 ( Subtotal = $418,043 )
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	6	5/6/2024	COMPETING CONTINUATION	$418,043
														Subtotal = $418,043

Issue Date FY: 2023 ( Subtotal = $402,046 )
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	001	5	5/22/2023	SUPPLEMENT FOR EXPANSION	$11,842
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	5	5/19/2023	NON-COMPETING CONTINUATION	$390,204
														Subtotal = $402,046

Issue Date FY: 2022 ( Subtotal = $390,204 )
2022	2022	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	4	5/26/2022	NON-COMPETING CONTINUATION	$390,204
														Subtotal = $390,204

Issue Date FY: 2021 ( Subtotal = $390,204 )
2021	2021	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	3	5/25/2021	NON-COMPETING CONTINUATION	$390,204
														Subtotal = $390,204

Issue Date FY: 2020 ( Subtotal = $515,204 )
2020	2020	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	2	4/29/2020	NON-COMPETING CONTINUATION	$390,204
2020	2020	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	001	2	9/4/2020	SUPPLEMENT FOR EXPANSION	$125,000
														Subtotal = $515,204

Issue Date FY: 2019 ( Subtotal = $390,204 )
2019	2019	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	1	7/23/2019	NEW	$390,204
														Subtotal = $390,204

Grand Total All Awards = $3,337,418

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Mechanisms of condensin-mediated gene regulation in C. elegans

Award Number: R35GM130311

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: 05/31/2029

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