# Enhancer RNAs and enhancer-centric gene regulatory networks in vascular dementia

> **NIH NIH R03** · UNIVERSITY OF SOUTH FLORIDA · 2024 · $150,000

## Abstract

Recent studies have reported widespread transcription of mammalian enhancers into noncoding RNAs in a
stimulus-dependent manner. Growing evidence shows that these RNAs, known as enhancer RNAs (eRNAs),
have essential roles in orchestrating higher-order chromatin interactions to facilitate gene expression and
phenotypic outcomes during development and disease. As a result, eRNAs are emerging as an important
component of the gene regulatory machinery. Due to their recent discovery, the expression, and roles of
eRNAs in vascular dementia are virtually unknown. Recently, we applied a combination of genome-wide RNA-
seq and genome-wide enhancer mapping using H3K27ac ChIP-seq to identify several ischemia-induced
eRNAs at multiple time-points of reperfusion in the mouse cerebral cortex. This was the first study on eRNAs in
brain vascular injury. We found an important role for one such eRNA in modulating post-stroke brain damage
and gene expression. In the current project, we will apply our expertise in eRNA discovery and function to
identify eRNAs that are expressed in the adult hippocampus specifically during the development of vascular
dementia. Using a standardized bilateral carotid artery stenosis (BCAS) model of vascular dementia, we will
induce hippocampal hypoperfusion in the mouse brain across a 30-day time-window. In Aim 1, we will use an
unbiased, genome-wide approach incorporating H3K27ac ChIP-seq and RNA-seq to map active enhancer
elements and their respective eRNAs from the earliest stages of cerebral hypoperfusion (day-3 post-BCAS) to
the manifestation of vascular dementia (day-30 post-BCAS). In Aim 2, along the same timeline we will apply
the cutting-edge method of Hi-C to capture genome-wide higher order chromatin interactions to pinpoint
enhancer-to-gene promoter contacts and map their dynamics along the BCAS trajectory. Together, this work
will identify novel enhancers and eRNAs that are activated specifically in response to BCAS-induced
hypoperfusion in the hippocampus and generate a catalog of putative enhancer-gene relationships that may
encompass regulatory networks. These data will lay the foundation for future mechanistic and functional
studies investigating these regulatory networks and their impact on the development of the hippocampal
pathophysiology and vascular dementia.

## Key facts

- **NIH application ID:** 10786221
- **Project number:** 1R03AG084918-01
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Ashutosh Dharap
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $150,000
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10786221

## Citation

> US National Institutes of Health, RePORTER application 10786221, Enhancer RNAs and enhancer-centric gene regulatory networks in vascular dementia (1R03AG084918-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10786221. Licensed CC0.

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