# Imaging enhancer-promoter interaction dynamics during embryonic brain development

> **NIH NIH R21** · TEXAS ENGINEERING EXPERIMENT STATION · 2020 · $193,429

## Abstract

Imaging enhancer-promoter interaction dynamics during embryonic brain development
During development, the vertebrate central nervous system is formed by partitioning proliferating primordial
cell populations into compartments and gradually refining these populations into distinct functional sub-re-
gions. Differentiation and organization of the various cell types in these regions are orchestrated by the expres-
sion of regulatory genes in precise spatial and temporal patterns. Gene expression, in particular its transcrip-
tion, is regulated primarily by enhancers, DNA sequences that activate transcription by interacting with gene
promoters. While much of what we understand about gene regulation by enhancers has been gained through
transgenesis assays and more recently through chromosome conformation capture and its next generation de-
rivatives, much is still unknown about how enhancers interact with gene promoters to activate transcription,
how dynamic and stable these interactions are, and how multiple enhancers interact with gene promoters and
each other. Thus, our understanding of cis-regulation may be advanced with the ability to characterize en-
hancer-promoter interaction dynamics. This project will develop the reagents and technologies to directly
measure the interactions among enhancer and promoter sequences in the fgf8a locus. Fgf8a is a morphogen
that regulates critical developmental processes including proliferation and positional identity and has been well
characterized in the developing brain and neural crest. In Aim 1, sequence specific probes will be developed
that do not interfere with normal fgf8a expression. In Aim 2, genetically encoded fluorescent protein variants
will be targeted to precise enhancer and promoter sequences in the genome. High resolution, selective plane
illumination microscopy with sub-diffraction-limited point source localization of the fluorophores will be used
to measure relative 3D spatial coordinates of the labeled sequences over time in the developing embryonic ver-
tebrate brain. This information will be used to better understand the dynamics and stability of enhancer-en-
hancer and enhancer-promoter interactions and its relationships with target gene transcription.

## Key facts

- **NIH application ID:** 9870971
- **Project number:** 5R21NS109504-02
- **Recipient organization:** TEXAS ENGINEERING EXPERIMENT STATION
- **Principal Investigator:** Holly Gibbs
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,429
- **Award type:** 5
- **Project period:** 2019-02-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870971

## Citation

> US National Institutes of Health, RePORTER application 9870971, Imaging enhancer-promoter interaction dynamics during embryonic brain development (5R21NS109504-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9870971. Licensed CC0.

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