# SWING LIGAND-REGULATED ENHANCER-DEPENDENT TRANSCRIPTION

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $118,500

## Abstract

ABSTRACT
In response to estrogen-dependent gene activation, the rapid assembly of the MegaTrans complex at responsive
enhancers, is suggested to assemble an RNP condensate with phase separation-like properties. The resultant
condensate is required for formation of homotypic cooperative enhancer networks, and initial data suggest that
these activated enhancers become rapidly associated with specific sub-nuclear bodies. Further, the enhanced
transcription of enhancers located separated by many TADs by linear distance may come into closer proximity
response to E2. Here, we hypothesize that by linking new mechanistic principles of ERα-bound enhancer, promoter
activation events to roles of transcription at chromosomal boundaries in chromosomal architectures and relocation into
specific subnuclear architectural structures, can provide mechanistic insights into the activation of large regulated
enhancer programs. First, we will explore a new approach to detect single strand DNA nicking genome-wide to
uncover a previously-overlooked, but required, mechanism for ligand- and signal-dependent acute activation of
enhancer programs. This would uncover a component of the DNA damage program that here instead serves as
required coactivators for regulated enhancer activation. We will test the hypothesis that the strongest
chromosomal boundaries harbor universally-expressed genes, and that they interact both intra- and inter-
chromosomally, impacting chromosomal architecture. This supports a functional association of active
chromosomal boundaries with specific subnuclear architectural structures. This R03 award would permit me to
generate the essential data required to establish new principles regarding dynamic enhancer activation programs
and interactions with specific subnuclear architectural structures for ligand-regulated gene transcriptional
programs, providing a strong experimental basis for subsequent submission of an R01 grant.

## Key facts

- **NIH application ID:** 10446924
- **Project number:** 1R03DK129217-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Dario Meluzzi
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $118,500
- **Award type:** 1
- **Project period:** 2022-04-04 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10446924

## Citation

> US National Institutes of Health, RePORTER application 10446924, SWING LIGAND-REGULATED ENHANCER-DEPENDENT TRANSCRIPTION (1R03DK129217-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10446924. Licensed CC0.

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