Year: 2023
Type: article
Abstract: Enhancer of zeste homolog 2 (EZH2) is an important transcriptional regulator in development that catalyzes H3K27me3. The role of EZH2 in epicardial development is still unknown. In this study, we show that EZH2 is expressed in epicardial cells during both human and mouse heart development.Ezh2epicardial deletion resulted in impaired epicardial cell migration, myocardial hypoplasia, and defective coronary plexus development, leading to embryonic lethality. By using RNA sequencing, we identified that EZH2 controls the transcription of tissue inhibitor of metalloproteinase 3 (TIMP3) in epicardial cells during heart development. Loss-of-function studies revealed that EZH2 promotes epicardial cell migration by suppressing TIMP3 expression. We also found that epicardialEzh2deficiency–induced TIMP3 up-regulation leads to extracellular matrix reconstruction in the embryonic myocardium by mass spectrometry. In conclusion, our results demonstrate that EZH2 is required for epicardial cell migration because it blocksTimp3transcription, which is vital for heart development. Our study provides new insight into the function of EZH2 in cell migration and epicardial development.
Source: Life Science Alliance
Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College, Fu Wai Hospital, First Affiliated Hospital Zhejiang University, State Key Laboratory of Cardiovascular Disease, Shanghai Institutes for Biological Sciences, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, State Key Laboratory of Cell Biology, Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences, State Key Laboratory of Medical Molecular Biology, Peking University, Center for Life Sciences
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,500
OpenAlex ID: W4362737293