Mechanisms of transcriptional condensate function during cell state transitions
Ended Project Grant Awarded Last action
- Award ID
- F31GM156078
- Recipient
-
The University Of Texas Southwestern Medical Center UEI YZJ6DKPM4W63 Part of University Of Texas System
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $121,303
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date
- Place of performance
- Dallas, TX 75390, USA
Award details come from USAspending.gov.
Description
- Abstract
- Dynamic rewiring of gene regulatory networks enables cell fate determination partly through differential gene expression. This process requires spatial organization of dozens of factors at precise genomic loci. Compartmentalization of transcription machinery into condensates-dynamic, mesoscale, local densities of proteins-has emerged as a mechanism coordinating this process. Although the function of condensates has been described in some cases, the mechanisms of their activity-particularly during cell fate determination- remain unclear. Many cell types are characterized by expression of cell-type-specific transcriptional regulators. The myocd coactivator is one such regulator for smooth muscle cell lineages. Using myocd as a case study, I have found that myocd-mediated gene activation and cell fate determination depend on switch-like, condensate formation. These studies also demonstrated the myocd trans-activation (TAD) domain is required for condensate formation and function. Surprisingly, substitution of the TAD domain for the intrinsically disordered regions (IDRS) of FUS or CDT1, two unrelated proteins known to form condensates, maintains condensate formation, but only substitution with the FUS-IDR activates gene expression. This indicates not only is self-association of the myocd coactivator essential for function, but that condensate formation mediated by distinct IDRS can exhibit distinct functionalities. I hypothesize coactivator condensates-mediated by different IDRS-confer distinct biochemical environments by directing genomic localization of gene expression machinery and selectively compartmentalizing transcriptional machinery into condensates to drive gene activation and cell fate determination. To address this hypothesis, I have developed an interdisciplinary and rigorous approach using various microscopy-, biochemical-, and sequencing-based experiments to model myocd-mediated condensate formation, gene activation and cell fate determination.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $564 | |
| Amendment | $40,485 | |
| Amendment | $40,127 | |
| Amendment | $40,127 | |
| Original award | $0 |
Quick answers
Who received award F31GM156078?
F31GM156078 was awarded to The University Of Texas Southwestern Medical Center by National Institute of General Medical Sciences (National Institutes of Health) on January 15, 2025.
How much is award F31GM156078 worth?
$121,303 has been obligated on F31GM156078.
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