# LncRNA mechanism of heart failure

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $549,746

## Abstract

Project Summary
The genome contains numerous non-coding DNA and RNA elements that far outnumber protein-
coding genes, presenting a drastically new perspective of the transcriptional circuits. Among
noncoding DNA elements, enhancers are the DNA fragments that activate target gene promoter by
acting on gene promoters, independent of their distance or orientation to target genes. Many
enhancers are recently found to encode noncoding RNAs, giving rise to an emerging class of
enhancer RNAs (eRNAs). The eRNA mechanisms of heart failure, particularly at its interface with
eDNA and chromatin, are largely unknown. We recently discovered a cardiac-specific eRNA capable
of protecting the heart against pathological hypertrophy and failure. This program will focus on new
mouse genetic models to define the molecular function of this newly identified eRNA in controlling
enhancer function, 3-dimensional chromatin looping, cardiac gene expression, and pathological
hypertrophy. Given that RNAs can be chemically modified and delivered as a drug for therapy, the
success of this program will lay down a foundation for designing new mechanism-based therapy.
Aim 1: Determining the in vivo sufficiency of an eRNA in cardioprotection. We will use transgenic and
knock in/out technology of mouse genetics to define the cardioprotective role of this eRNA. Methods
include CRISPR-enabled inducible and cardiomyocyte-specific eRNA modifications, transaortic
constriction, histopathology, echocardiography, pressure-volume loop, and molecular marker studies.
Aim 2: Defining how an eRNA interacts with its cognate eDNA in 3-dimensional chromatin looping
and gene regulation. We will determine molecular interactions between an eRNA and its cognate
eDNA in forming eRNA-eDNA hybrid duplex and in chromatin looping to target genes for transcription
regulation under different pathophysiological conditions. Methods include mouse genetics, chromatin
conformation capture, quantitative PCR, helicase assay, electric mobility shift assays, and DNA-RNA
duplex immunoprecipitation.
Aim 3: Defining eRNA-eDNA interactions in normal and diseased human hearts. We will use human
heart tissues and iPS-derived cardiomyocytes to define the evolutionary conservation of eRNA-eDNA
interactions and eDNA three-dimensional chromatin looping to target genes. Methods include
ribosome profiling, in vitro transcription and translation, qPCR, chromatin fractionation and
conformation capture, DNA-RNA duplex immunoprecipitation, and iPS-based technology.

## Key facts

- **NIH application ID:** 10228684
- **Project number:** 5R01HL121197-08
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** CHING-PIN CHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $549,746
- **Award type:** 5
- **Project period:** 2020-06-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228684

## Citation

> US National Institutes of Health, RePORTER application 10228684, LncRNA mechanism of heart failure (5R01HL121197-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10228684. Licensed CC0.

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