GATA-4 regulates cardiac morphogenesis through transactivation of the N-cadherin gene.
Cardia bifida is known to occur in animal models lacking the cardiogenic transcriptional factor GATA-4. The downstream target genes responsible for this cardiac deformity remain unknown, however. Treatment with small interfering RNAs (siRNA) specifically targeting GATA-4 into cardiac mesodermal cells led to the development of cardia bifida in chick embryos. RT-PCR using mRNAs extracted from cardiac tubes revealed that the GATA-4-specific siRNA selectively suppresses expression of N-cadherin mRNA, one of the genes essential for the single heart formation, without affecting other cardiac marker mRNAs. Analysis of the N-cadherin gene promoter activity using a luciferase reporter gene system and electrophoretic mobility shift assays revealed that GATA-4 binds directly to the N-cadherin gene promoter region, thereby transactivating its expression. We therefore concluded that the cardia bifida observed in the GATA-4-deleted model is caused by the transcriptional down-regulation of N-cadherin expression.
Zhang
Hong
H
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, 565-0871, Osaka, Japan.
Toyofuku
Toshihiko
T
Kamei
Junko
J
Hori
Masatsugu
M
D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism*; D002642:Chick Embryo; D002645:Chickens; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D050991:GATA4 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology* / Q000254:growth & development*; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis; D009206:Myocardium / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*
D015820:Cadherins; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D014157:Transcription Factors