# The role of transcription factor Ying-Yang 1 in the cardiac bioenergetics regulation

> **NIH NIH R03** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $79,500

## Abstract

Project summary
 Pathological cardiac stress induces transcriptional reprogramming leading to
maladaptive phenotypes, including metabolic impairment. A hallmark of metabolic
derangement in heart failure is the suppressed expression of a network of nuclear
transcription factors controlling metabolic genes transcription, including Peroxisome
proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). PGC-1α is the
master regulator of mitochondrial biogenesis and oxidative phosphorylation. On the
contrast, cardiac PGC-1α expression and bioenergetics are upregulated in response to
endurance exercise. To date, the mechanisms of the regulation of PGC-1α in cardiac
stress response are still poorly understood. My K08 research project focused on
investigating the role of Brain-derived Neurotrophic Factor (BDNF) in the regulation of
cardiac energetics. We found that Yin-Yang transcription factor (YY1), a multi-functional
transcription factor, plays a critical role in BDNF-induced PGC-1α expression and
metabolism in cultured cardiomyocytes. However, the precise role of YY1 in cardiac
bioenergetics regulation in vivo is largely unknown. Our preliminary data showed that YY1
expression was upregulated in the hearts subjected to endurance exercise as well as in
failing hearts. Therefore, there is a discrepancy between YY1 and PGC-1α expression.
YY1 acts as transcriptional activator and repressor depending on surrounding epigenetic
proteins or transcription co-factors. It is known that acetylation of YY1 through
acetyltransferase p300 leads to transcriptional activation of downstream genes, whereas
deacetylation of YY1 through histone deacetylases (HDACs) leads to transcriptional
repression. Our preliminary data showed that HDAC inhibition increased PGC-1α
expression in heart failure. In this proposal, we will test the hypothesis that the YY1 plays
an essential role in cardiac bioenergetics in cardiac stress response through PGC-1α
expression regulation, and the regulation of PGC-1α expression by YY1 is determined by
dynamic acetylation.

## Key facts

- **NIH application ID:** 10504503
- **Project number:** 1R03HL164393-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Ning Feng
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $79,500
- **Award type:** 1
- **Project period:** 2022-08-22 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10504503

## Citation

> US National Institutes of Health, RePORTER application 10504503, The role of transcription factor Ying-Yang 1 in the cardiac bioenergetics regulation (1R03HL164393-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10504503. Licensed CC0.

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