# Transcriptional regulation of BEST1 in retina pigment epithelium.

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $399,058

## Abstract

Abstract
The overarching goal of this study is to understand how BEST1 expression is modulated by cis-regulatory
elements in the retinal pigment epithelium (RPE). The variability of retinal phenotypes and age of onset of
visual loss, even in individuals who carry the same causative mutation, is one of the biggest mysteries for
BEST1 related diseases. Genetic variations in non-coding regulatory elements can serve as an attractive
model to provide the molecular basis for the observed various onsets of BEST1 vitelliform macular dystrophy
(BVMD) in patients. Therefore understanding the transcriptional control mediated by cis-regulatory elements in
the RPE will give us insight into novel target regions for therapeutic editing of the enhancer elements identified
by this study. We are utilizing human induced pluripotent stem cells (iPSCs)-derived RPEs as a model to
understand cell type-specific transcriptional controls of BEST1. We are also utilizing integrative, unbiased, and
high throughput epigenomic and genetic tools to achieve the following aims: (1) We will use a high resolution
4C-seq analysis to identify potential regulatory elements that interact with the BEST1 promoter in human
primary RPE. (2) In Aim 2, we will generate BEST1 dual allele reporter lines and use these lines to interrogate
cis-regulatory elements of BEST1 in their native chromatin contexts utilizing high throughput CRIPSR/Cas9
mediated genome editing approach. (3) Finally, we will test the utilities of allelic specific enhancer deletion to
modulate allelic expression of BEST1. We expect these analyses will significantly advance our knowledge of
the precise control of BEST1 transcription in RPEs.

## Key facts

- **NIH application ID:** 10200053
- **Project number:** 5R01EY027789-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Yin Shen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $399,058
- **Award type:** 5
- **Project period:** 2017-09-30 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200053

## Citation

> US National Institutes of Health, RePORTER application 10200053, Transcriptional regulation of BEST1 in retina pigment epithelium. (5R01EY027789-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10200053. Licensed CC0.

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