# Cell-type– and developmental stage–specific regulation of gene expression in the retina

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2021 · $435,287

## Abstract

PROJECT SUMMARY
 During retinal development, more than 8,000 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 changes in the covalent modifications to the DNA and
histones and higher-order DNA looping accompany changes in gene expression, little is known about
how those processes are coordinated during retinal development. Over the past 5 years, we developed
a detailed map of the structure and accessibility of the human and mouse retinal genome during
development. Specifically, we performed a multifaceted integrated analysis that included profiling of the
covalent modifications to the DNA and histones, promoter structure, chromatin accessibility, looping
interactions, and euchromatin/heterochromatin localization. All these published and unpublished data
are shared freely with the biomedical research community through our integrated retinal nucleome
database (iRNDb) (https://pecan.stjude.cloud/retinalnucleome). One of the most significant discoveries
to come from the iRNDb was the identification of a series of core regulatory circuit super-enhancers
(CRC-SEs) adjacent to genes having important roles in retinal development, including Vsx2, Crx, Six3,
Otx2, Fgf15, and Ascl1. The CRC-SE upstream of the Vsx2 gene was particularly exciting because it
had activity consistent with bipolar cell development. We deleted the Vsx2-CRC-SE in mice and
showed that bipolar neurons are absent yet all other cell types develop normally. Importantly, retinal
progenitor cell proliferation was normal, indicating that we had separated the bipolar cell regulatory
elements from that of retinal progenitor cells. In this proposal, we will elucidate the structure and
organization of the Vsx2 CRC-SE, identify other transcription factors that may cooperate with Vsx2 to
regulate bipolar cell type–specific expression and test the consequences of loss of bipolar cells on
other cell types in the retina. The results of these studies will be important for filling a fundamental gap
in our knowledge about the role of CRC-SEs in retinal development and will set the stage for
characterization of CRC-SEs in other genes required for retinogenesis. All published and unpublished
data are shared through the iRNDb to accelerate discovery on retinal development and disease.

## Key facts

- **NIH application ID:** 10089458
- **Project number:** 5R01EY030180-02
- **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:** 2021
- **Award amount:** $435,287
- **Award type:** 5
- **Project period:** 2020-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10089458

## Citation

> US National Institutes of Health, RePORTER application 10089458, Cell-type– and developmental stage–specific regulation of gene expression in the retina (5R01EY030180-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10089458. Licensed CC0.

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