Project Grant DP2GM150021

Award Date 9/1/22
Completion Date 8/31/25
Dollars Obligated $3M
Federal Grant Program
93.859
Assistance Type
Project Grant
Place of Performance
New York, NY 10065, USA
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This $2,970,082 Project Grant from the Department of Health and Human Services' Assistant Secretary for Financial Resources, under the National Institute of General Medical Sciences' Biomedical Research and Research Training program (CFDA 93.859), will support research into the cross-regulation between loop extrusion, chromatin fiber structure, and chromatin-associated RNAs in mammalian genomes.

The awardee, Rockefeller University, will conduct experiments from September 2022 to August 2025 to probe how loop extrusion by the cohesin complex perturbs local chromatin fiber structure; how the structure of the chromatin fiber regulates cohesin's ability to load and extrude loops; how changes in supercoiling from excess cohesin looping affect nucleosome interactions; and the chromatin-associated RNA interactome of CTCF at RNA-dependent and -independent loop boundaries. A combination of protein depletion, degradation, and pharmacological inhibition methods will be used in human and mouse cell lines, with outcomes measured via RICC-SEQ and novel techniques to probe chromatin-associated RNA interactomes. Epigenome and transcription profiling tools and coarse-grained simulations will also be employed to develop multi-scale models of the interaction between loop extrusion machinery and chromatin fiber.

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