[The mechanism of TBX5 abnormal expression in simple congenital heart disease]

Yi Chuan. 2009 Apr;31(4):374-80. doi: 10.3724/sp.j.1005.2009.00374.
[Article in Chinese]

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.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • CpG Islands / genetics
  • DNA Methylation / genetics
  • Electrophoretic Mobility Shift Assay
  • Female
  • Heart Defects, Congenital / genetics*
  • Humans
  • Infant, Newborn
  • Mice
  • Pregnancy
  • Promoter Regions, Genetic / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / physiology*

Substances

  • T-Box Domain Proteins
  • T-box transcription factor 5