Yanyan Qian1,2, Deyong Xiao1, Xiao Guo2, Hongbo Chen2, Lili Hao1, Xiaojing Ma3, Guoying Huang2,3, Duan Ma1,2, Huijun Wang2. 1. Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Collaborative Innovation Center of Genetics and Development, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China. 2. Shanghai Key Lab of Birth Defects, Pediatrics Research Institute, Children's Hospital of Fudan University Shanghai, China. 3. Pediatric Heart Center, Children's Hospital of Fudan University, Shanghai, China.
Abstract
BACKGROUND: BRG1, an ATPase subunit of the SWItch/Sucrose Non-Fermentable complex, is tightly associated with cardiac development. However, little is known about the association between the pathogenesis of CHD and BRG1. METHODS: The methylation of a BRG1 promoter and a novel CpG island in the second intron was analyzed in the myocardium of congenital heart disease (CHD) patients (n = 24) and normal controls (n = 11) using pyrosequencing and the MassARRAY platform. BRG1 expression was sketched in the normal fetal and postnatal heart using real-time PCR. BRG1 mRNA and protein expression was detected by means of real-time PCR and immunohistochemistry. The expression of GATA4 was analyzed with real-time PCR. RESULTS: The CpG shore in the second intron of BRG1 was hypomethylated in the myocardium of patients (p < 0.05). BRG1 showed a high level of expression in the normal fetal heart in the second trimester (p < 0.01). Compared with that of the normal subjects, BRG1 expression was decreased by 70% in the myocardium of patients (n = 92; p < 0.05). Of note, the expression of GATA4 was significantly correlated with BRG1 expression (r = 0.7475; p = 0.0082) in the myocardium, and it was also decreased by 70% in these patients (n = 92; p < 0.05). CONCLUSION: These results suggested that the early high expression of BRG1 in fetal hearts maintained normal cardiac development and that the abnormal hypomethylation and decreased expression of BRG1 in human hearts probably affect the expression of GATA4, which affects the pathogenesis of CHD. Birth Defects Research 109:1183-1195, 2017.
BACKGROUND:BRG1, an ATPase subunit of the SWItch/Sucrose Non-Fermentable complex, is tightly associated with cardiac development. However, little is known about the association between the pathogenesis of CHD and BRG1. METHODS: The methylation of a BRG1 promoter and a novel CpG island in the second intron was analyzed in the myocardium of congenital heart disease (CHD) patients (n = 24) and normal controls (n = 11) using pyrosequencing and the MassARRAY platform. BRG1 expression was sketched in the normal fetal and postnatal heart using real-time PCR. BRG1 mRNA and protein expression was detected by means of real-time PCR and immunohistochemistry. The expression of GATA4 was analyzed with real-time PCR. RESULTS: The CpG shore in the second intron of BRG1 was hypomethylated in the myocardium of patients (p < 0.05). BRG1 showed a high level of expression in the normal fetal heart in the second trimester (p < 0.01). Compared with that of the normal subjects, BRG1 expression was decreased by 70% in the myocardium of patients (n = 92; p < 0.05). Of note, the expression of GATA4 was significantly correlated with BRG1 expression (r = 0.7475; p = 0.0082) in the myocardium, and it was also decreased by 70% in these patients (n = 92; p < 0.05). CONCLUSION: These results suggested that the early high expression of BRG1 in fetal hearts maintained normal cardiac development and that the abnormal hypomethylation and decreased expression of BRG1 in human hearts probably affect the expression of GATA4, which affects the pathogenesis of CHD. Birth Defects Research 109:1183-1195, 2017.
Authors: Naikhoba C O Munabi; Shady Mikhail; Omar Toubat; Michelle Webb; Allyn Auslander; Pedro A Sanchez-Lara; Zarko Manojlovic; Ryan J Schmidt; David Craig; William P Magee; Subramanyan Ram Kumar Journal: Am J Med Genet A Date: 2022-04-06 Impact factor: 2.578