# Novel Mechanisms of LncRNA Mediated Epigenetic Regulation in Cardiac Hypertrophy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $537,696

## Abstract

Abstract
 Transcriptome reprogramming is central to cardiac hypertrophy and pathological remodeling. Recent
advances in genomics have dramatically expanded the scope and function of the cardiac transcriptome to cover
much beyond the coding genes to include many non-coding genes. In particular, a vast cohort of long non-coding
RNAs (so called lncRNAs) have been identified in cardiac transcriptome, yet, much of their functions remain
unexplored. In preliminary studies leading to this proposal, we discovered a novel cardiac-enriched lncRNA
expressed in mouse, rat and human heart which is demonstrated to be essential to pressure overload-induced
cardiac hypertrophy. Furthermore, we demonstrated that this lncRNA interacts specifically with the chromatin
modifying complex PRC2 to modulate H3K27me2/3 levels on pathological genes in stressed heart, thus we
named this lncRNA as Cardiac Hypertrophy Associated Epigenetic Regulator (Chaer). Most intriguingly, we
found Chaer transiently interacts with PRC2 transient at the onset of hypertrophic stimulation in an mTOR
dependent manner. This transient interaction appears to be important to the early onset but not the subsequent
progression of cardiac hypertrophy and heart failure. Therefore, the Chaer-PRC2 interaction appears to be an
early epigenetic check-point necessary for hypertrophic gene expression and remodeling in the heart. This
discovery highlights two potentially very important roles for lncRNAs in transcription regulation: one as a
molecular switch to link epigenetic modifiers with cellular stress signals, and another as a molecular chaperon
to orchestrate target specificity in the context of specific tissues for ubiquitous epigenetic modifiers. To further
establish this novel concept, we propose to vigorously investigate the mechanism of Chaer mediated cardiac
gene regulation by achieving the following three specific aims: Aim 1. To uncover the molecular basis for
hypertrophic signal regulated interaction between Chaer and PRC2. Aim 2. To investigate how Chaer
interaction regulates Ezh2 function in response to hypertrophic stimulation. Aim 3. To establish the
functional impact of Chaer-PRC2 interaction on cardiac epigenetic modulation and transcriptome
reprogramming during cardiac hypertrophy. Accomplishing these aims will fill a major gap in our current
knowledge of epigenetic regulation in cardiac hypertrophy and advance our mechanistic understanding of
inducible, locus-specific chromatin modification in heart cells.

## Key facts

- **NIH application ID:** 9962480
- **Project number:** 5R01HL143058-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Thomas M. Vondriska
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $537,696
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962480

## Citation

> US National Institutes of Health, RePORTER application 9962480, Novel Mechanisms of LncRNA Mediated Epigenetic Regulation in Cardiac Hypertrophy (5R01HL143058-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9962480. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*