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EZH2-mediated H3K27me3 inhibits ACE2 expression.
Li, Yuanyuan; Li, Honggang; Zhou, Liquan.
  • Li Y; Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Li H; Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: lhgyx@hotmail.com.
  • Zhou L; Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zhouliquan@hust.edu.cn.
Biochem Biophys Res Commun ; 526(4): 947-952, 2020 06 11.
Article in English | MEDLINE | ID: covidwho-38740
ABSTRACT
The outbreak of corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is spreading globally and quickly, leading to emerging health issues. SARS-CoV-2 enters into and infects host cells through its spike glycoprotein recognizing the cell receptor Angiotensin-converting enzyme II (ACE2). Here, we noticed that ACE2 was further enhanced by SARS-CoV-2 infection. Human germ cells and early embryos express high level of ACE2. Notably, RNA-seq result showed that reduction of H3K27me3, but not H3K4/9/36me3, led to upregulation of Ace2 expression in mouse germ cell line GC-2. In agreement with this result, we found in human embryonic stem cells that ACE2 expression was significantly increased in absence of EZH2, the major enzyme catalyzing H3K27me3. ChIP-seq analysis further confirmed decrease of H3K27me3 signal and increase of H3K27ac signal at ACE2 promoter upon EZH2 knockout. Therefore, we propose that EZH2-mediated H3K27me3 at ACE2 promoter region inhibits ACE2 expression in mammalian cells. This regulatory pattern may also exist in other human cells and tissues. Our discovery provides clues for pathogenesis and targeted drug therapy towards ACE2 expression for prevention and adjuvant therapy of COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Gene Expression Regulation / Coronavirus Infections / Peptidyl-Dipeptidase A / Epigenesis, Genetic / Enhancer of Zeste Homolog 2 Protein / Betacoronavirus Limits: Animals / Humans Language: English Journal: Biochem Biophys Res Commun Year: 2020 Document Type: Article Affiliation country: J.bbrc.2020.04.010

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Gene Expression Regulation / Coronavirus Infections / Peptidyl-Dipeptidase A / Epigenesis, Genetic / Enhancer of Zeste Homolog 2 Protein / Betacoronavirus Limits: Animals / Humans Language: English Journal: Biochem Biophys Res Commun Year: 2020 Document Type: Article Affiliation country: J.bbrc.2020.04.010