# See-ing the 4D Nucleome: Enhancer Cooperativity in Phase Separated Structures

> **NIH NIH K01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $118,206

## Abstract

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PROJECT ABSTRACT
The central goal of this proposal is to shed new light on the roles of chromosomal architecture and phase
separation in regulation of gene transcriptional programs by liganded nuclear receptors, and to use this project
and the experimental skills acquired to transition to an academic career as an independent investigator studying
the mechanisms underlying regulated gene transcriptional programs. My focus is on gene enhancers. I will
examine a cohort of active MegaTrans-bound enhancers separated by vast genomic distances and use several
approaches to investigate whether E2 induces rapid changes in chromosomal architecture, resulting in spatial
proximity and chromosome-wide cooperativity of these enhancers. Two new ideas, the possible condensin-
dependency of this inter-TAD enhancer association and cooperation and the potential role of phase separation
events occurring between MegaTrans enhancers and RNP nuclear structures, including inter-chromatin granules
(ICGs) will be specifically investigated. Finally, I propose to develop and utilize contemporary real time imaging
and accompanying informatics approaches to uncover the functional alterations in chromosomal and subnuclear
architectural structures induced by estrogen. Together, this approach can significantly alter our current concepts
about regulated gene transcriptional programs.

## Key facts

- **NIH application ID:** 10003028
- **Project number:** 5K01DK119687-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Dario Meluzzi
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $118,206
- **Award type:** 5
- **Project period:** 2018-09-07 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003028

## Citation

> US National Institutes of Health, RePORTER application 10003028, See-ing the 4D Nucleome: Enhancer Cooperativity in Phase Separated Structures (5K01DK119687-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10003028. Licensed CC0.

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