# Enhancer Connectomes in Regulation of Gene Expression

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $456,822

## Abstract

PROJECT ABSTRACT
A fundamental question in regulatory biology is whether enhancers regulate only the coding target genes with
spatial proximity, or whether they regulate chromosomal architecture, exerting transcriptional effects on genes
far removed in a specific chromosome. Thus, in addition to exhibiting regulated interactions with its cognate
promoter, and perhaps with other enhancers in a single TAD, it is important to solve whether signal-induced
proximity of specific robustly-activated regulatory enhancers, separated by vast linear distances within a
chromosome, constitute a “first tier” network that alters the transcription of specific, interacting component
enhancers. We hypothesize that this ”first tier” network, while not impacting the ability of each component
enhancer to loop to and activate its cognate target coding gene promoter, nucleates formation of an
architectural “structure” that provides the machinery that licenses the robustness of the transcriptional
response imparted by these individual enhancers. We will use both GRO-seq and assays of 3D architecture to
test whether conceptualize a ligand-dependent distributive superenhancer connectome dictates chromosomal
architecture. This would represent an entirely new perspective on enhancer networks, revealing interactions of
E2-regulated enhancers that modulate whole chromosome architecture and ensemble chromosomal structures
result in an unexpected integrated transcriptional response network based on actions of single, robust “first
tier” enhancers.

## Key facts

- **NIH application ID:** 10073501
- **Project number:** 5R01DK018477-45
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** MICHAEL G ROSENFELD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $456,822
- **Award type:** 5
- **Project period:** 1998-10-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073501

## Citation

> US National Institutes of Health, RePORTER application 10073501, Enhancer Connectomes in Regulation of Gene Expression (5R01DK018477-45). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10073501. Licensed CC0.

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