PERM1 regulates genes involved in fatty acid metabolism in the heart by interacting with PPARα and PGC-1α

Chun yang Huang, Shin ichi Oka, Xiaoyong Xu, Chian Feng Chen, Chien Yi Tung, Ya Yuan Chang, Youssef Mourad, Omair Vehra, Andreas Ivessa, Ghassan Yehia, Peter Romanienko, Chiao Po Hsu, Junichi Sadoshima*

*此作品的通信作者

研究成果: Article同行評審

5 引文 斯高帕斯(Scopus)

摘要

PERM1 (PGC-1/ERR-induced regulator in muscle 1) is a muscle-specific protein induced by PGC-1 and ERRs. Previous studies have shown that PERM1 promotes mitochondrial biogenesis and metabolism in cardiomyocytes in vitro. However, the role of endogenous PERM1 in the heart remains to be investigated with loss-of-function studies in vivo. We report the generation and characterization of systemic Perm1 knockout (KO) mice. The baseline cardiac phenotype of the homozygous Perm1 KO mice appeared normal. However, RNA-sequencing and unbiased pathway analyses showed that homozygous downregulation of PERM1 leads to downregulation of genes involved in fatty acid and carbohydrate metabolism in the heart. Transcription factor binding site analyses suggested that PPARα and PGC-1α are involved in changes in the gene expression profile. Chromatin immunoprecipitation assays showed that PERM1 interacts with the proximal regions of PPAR response elements (PPREs) in endogenous promoters of genes involved in fatty acid oxidation. Co-immunoprecipitation and reporter gene assays showed that PERM1 promoted transcription via the PPRE, partly in a PPARα and PGC-1α dependent manner. These results suggest that endogenous PERM1 is involved in the transcription of genes involved in fatty acid oxidation through physical interaction with PPARα and PGC-1α in the heart in vivo.

原文English
文章編號14576
期刊Scientific reports
12
發行號1
DOIs
出版狀態Published - 12月 2022

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