# The Role of Modular Super-Enhancers in the Developing Murine and Human Retina

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2024 · $596,514

## Abstract

PROJECT SUMMARY
 During retinal development, thousands of genes change in their expression as multipotent retinal
progenitor cells produce each of the 7 classes of cell types in an evolutionarily conserved birth order.
Although it has been well established that large enhancers called super-enhancers (SEs) can play an
important role in regulating developmental stage– and cell type–specific gene expression, a major
barrier in the field is identifying specific promoter-SE interactions. This is challenging because SEs can
act over long distance (up to 1 Mb) and in either orientation. For convenience, investigators often
assume that the closest SE is the most relevant, but this is often not the case. Identification and
characterization of specific promoter–SE interactions are important because mutations in the non-
coding genome can contribute to human disease including retinopathies. To address this major gap in
knowledge, we have spent the past 10 years developing a detailed map of chromatin structure in the
developing human and murine retinae. This integrated retinal nucleome database (iRNDb) is the largest
and most comprehensive map of chromatin structure in the retina with over 2,500 individual files.
Recently, we updated the iRNDb (v.2) with the addition of single cell RNA-seq and single cell ATAC-
seq to provide developmental stage– and cell type–specific features and HiChIP to provide data on
promoter–SE interactions. All our published and unpublished data are shared freely with the biomedical
research community on the St. Jude Cloud (https://proteinpaint.stjude.org/iRNDb_v2). Using the iRNDb
(v.2), we have identified developmental stage– and cell type–specific promoter–SE interactions for
each of the early retinal transcription factor network genes (Vsx2, Lhx2, Otx2, Pax6, Rax, Six3, Six6,
Sox2 and Tbx3). The most exciting discovery is that each of the SEs associated with the early retinal
transcription factor genes is made up of discrete modules predicted to have developmental stage– and
cell type–specific activity. In this proposal, we will test the hypothesis that Six3/SIX3 and Otx2/OTX2
are regulated by modular SEs in human and murine retinae. These genes were chosen because they
are essential for retinogenesis and altered expression can cause developmental defects in humans.
Our results will fill a fundamental gap in our knowledge about the regulation of early retinal transcription
factor network genes and validate our genome-wide map of promoter–SE interactions in the developing
retina (iRNDb (v.2)). This research proposal is relevant to human health because it will provide a map
of relevant regulatory elements in the non-coding genome that may contribute to developmental
defects.

## Key facts

- **NIH application ID:** 10994780
- **Project number:** 1R01EY036689-01
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Michael A Dyer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $596,514
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10994780

## Citation

> US National Institutes of Health, RePORTER application 10994780, The Role of Modular Super-Enhancers in the Developing Murine and Human Retina (1R01EY036689-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10994780. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*