Kai-yuan Ji
Jian Zhang
Yanxia Xu
Yue Ying
Taoyi Mai
Shuxiang Xu
Qian-bing Zhang
Kai-tai Yao
Yang Xu
1 Cancer Research Institute, Guangdong Provincial Key Laboratory of Cancer Immunotherapy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China;
2 The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong, China
Funds: This study was supported by National Natural Science Foundation of China (81430032, U1601222), the leading talents of Guangdong Province Program (No. 00201516), the Key Research and Development Program of Guangdong Province (2019B020235003), Guangdong Provincial Key Laboratory of Cancer Immunotherapy, Major basic research developmental project of the Natural Science Foundation of Guangdong Province (2014A030308018), Science and Technology Innovation Committee of Shenzhen Municipality (JCYJ20180504170301309), and Shenzhen "Sanming" Project of Medicine (SZSM201602102).
Received Date: 2019-02-17
Rev Recd Date:2019-04-15
Abstract
Abstract
Human embryonic stem cells (hESCs) depend on glycolysis for energy and substrates for biosynthesis. To understand the mechanisms governing the metabolism of hESCs, we investigated the transcriptional regulation of glucose transporter 1 (GLUT1, SLC2A1), a key glycolytic gene to maintain pluripotency. By combining the genome-wide data of binding sites of the core pluripotency factors (SOX2, OCT4, NANOG, denoted SON), chromosomal interaction and histone modification in hESCs, we identified a potential enhancer of the GLUT1 gene in hESCs, denoted GLUT1 enhancer (GE) element. GE interacts with the promoter of GLUT1, and the deletion of GE significantly reduces the expression of GLUT1, glucose uptake and glycolysis of hESCs, confirming that GE is an enhancer of GLUT1 in hESCs. In addition, the mutation of SON binding motifs within GE reduced the expression of GLUT1 as well as the interaction between GE and GLUT1 promoter, indicating that the binding of SON to GE is important for its activity. Therefore, SON promotes glucose uptake and glycolysis in hESCs by inducing GLUT1 expression through directly activating the enhancer of GLUT1.Keywords: human embryonic stem cell,
pluripotency factors,
metabolism,
Glut1,
enhancer,
promoter,
epigenetics,
chromosome interaction
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