CpG site hypomethylation at ETS1-binding region regulates DLK1 expression in Chinese patients with Tetralogy of Fallot
| Autor: | Guixiang Tian, Lili He, Ruoyi Gu, Jingwei Sun, Weicheng Chen, Yanyan Qian, Xiaojing Ma, Weili Yan, Zhenshan Zhao, Ziqing Xu, Meijiao Suo, Wei Sheng, Guoying Huang |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Male
Cancer Research China δ like non-canonical Notch ligand 1 Biochemistry Proto-Oncogene Protein c-ets-1 Asian People Genetics Humans Promoter Regions Genetic Molecular Biology DNA methylation Binding Sites Base Sequence Calcium-Binding Proteins Infant Membrane Proteins Articles Sequence Analysis DNA HEK293 Cells Oncology Gene Expression Regulation Child Preschool Tetralogy of Fallot Molecular Medicine ETS proto-oncogene 1 CpG Islands Female Protein Binding |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart malformation accounting for ~10% of cases. Although the pathogenesis of TOF is complex and largely unknown, epigenetics plays a huge role, specifically DNA methylation. The protein δ like non-canonical Notch ligand 1 (DLK1) gene encodes a non-canonical ligand of the Notch signaling pathway, which is involved in heart development. However, the epigenetic mechanism of DLK1 in the pathogenesis of TOF is yet to be elucidated. Therefore, the present study aimed to clarify its specific mechanism. In this study, immunohistochemistry was used to detect the protein expression of DLK1 and the methylation status of the DLK1 promoter was measured via bisulfite sequencing PCR. Dual-luciferase reporter assays were performed to examine the influence of transcription factor ETS proto-oncogene 1 (ETS1) on DLK1 gene expression. The electrophoretic mobility shift assay and chromatin immunoprecipitation assay, both in vivo and in vitro, were used to verify the binding of the ETS1 transcription factor to the DLK1 promoter as well as the influence of methylation status of DLK1 promoter on this binding affinity. The expression of DLK1 in the right ventricular outflow tract was significantly lower in patients with Tetralogy of Fallot (TOF) than that in controls (P |
| Databáze: | OpenAIRE |
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