# Mechanisms of Transcriptional Condensate Function during Cell State Transitions

> **NIH NIH F31** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $40,127

## Abstract

Project Summary
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.

## Key facts

- **NIH application ID:** 10996524
- **Project number:** 1F31GM156078-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Mikayla Eppert
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,127
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996524

## Citation

> US National Institutes of Health, RePORTER application 10996524, Mechanisms of Transcriptional Condensate Function during Cell State Transitions (1F31GM156078-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10996524. Licensed CC0.

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