title: [The mechanism of TBX5 abnormal expression in simple congenital heart disease].
abstract: To explore the mechanism of TBX5 abnormal expression in simple congenital heart disease (CHD), 100 CHD venous blood, 50 CHD heart tissues, and 5 non-CHD heart tissues were involved in this study. The mutation and methylation in the 1 200 bp region upstream of TBX5 gene were detected by high-performance liquid chromatography (DHPLC) and methylation-sensitive restriction endonuclease (MS-RE), respectively. The binding site of NKX2-5 to Tbx5 predicted by P-MATCH software was validated by EMSA (Electrophoretic mobility shift assay). Tbx5 gene expression in mouse cardiac muscle cell H9C2(2-1) transfected with NKX2-5 expression vector was evaluated. No mutation was found in all patients. Both non-CHD and CHD heart tissues had the same methylation in the two CpG islands. Exogenous Nkx2-5 efficiently activated the transcription of the endogenous Tbx5 gene in H9C2 (2-1) cells. EMSA showed that the special binding band appeared when Nkx2-5 existed. These results indicates that the down expression of TBX5 might not be caused by mutation and methylation in the 1 200 bp region upstream of gene, and might be regulated by abnormal expression of NKX2-5 gene in heart muscle of CHD.
authors: Department of Medical Genetics, China Medical University, Shenyang 110001, China. znnadi@163.com
authors: Na
authors: N
authors: Xin
authors: Guang-Rong
authors: GR
authors: Qiu
authors: Li-Guo
authors: LG
authors: Gong
authors: Xiao-Yan
authors: XY
authors: Xu
authors: Kai-Lai
authors: KL
authors: Sun
mesh_terms: D000818:Animals; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5