# Gene Regulatory Non-Coding RNAs in the Human Heart

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $585,828

## Abstract

This collaborative proposal from a cardiac molecular geneticist and a
RNA-chromatin biochemist will investigate chromatin associated and
transcription factor dependent non-coding RNAs (ncRNAs) as essential
components of a cardiac regulatory network. We have applied a novel approach
for identification of functional long non-coding RNAs (lncRNAs) and the
enhancers that comprise gene regulatory networks. Using transcription factor-
dependence, we identified ncRNAs as markers of cis-regulatory elements
essential for a mouse cardiac rhythm gene regulatory network. This approach
identified exceptionally strong enhancers, and their associated ncRNA are
chromatin-bound and required for enhancer function. This proof of principal sets
the stage for the investigation of lncRNAs and their associated enhancers in
human cardiac gene regulatory networks. We posit that application of our
approach to human cardiomyocytes will allow identification of a functional class
of human heart enhancer-associated lncRNAs and cis-regulatory elements
(CREs) essential for the expression of human cardiac rhythm control genes. In
the first specific aim, we will interrogate a set of lncRNAs defined by their TF-
dependence and chromatin localization for their requirement for CRE activity and
target gene expression. In the second aim, we will utilize novel molecular tools
to probe the molecular mechanisms whereby the lncRNAs modulate gene
expression. Together these interconnected aims rely on the complementary and
non-overlapping expertise of the collaborative investigators to address a highly
significant problem in ncRNA biology. These hypotheses are applicable to
human genetics, transcriptional regulation, and RNA biology, and therefore may
have impact both within cardiovascular genetics and more broadly within human
molecular genetics.

## Key facts

- **NIH application ID:** 9996779
- **Project number:** 5R01HL148719-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Ivan Paul Moskowitz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $585,828
- **Award type:** 5
- **Project period:** 2019-08-17 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996779

## Citation

> US National Institutes of Health, RePORTER application 9996779, Gene Regulatory Non-Coding RNAs in the Human Heart (5R01HL148719-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9996779. Licensed CC0.

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