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Hammer, Stefanie; Toenjes, Martje; Lange, Martin; Fischer, Jenny J.; Dunkel, Ilona; Mebus, Siegrun; Grimm, Christina H.; Hetzer, Roland; Berger, Felix; Sperling, Silke

Characterization of TBX20 in human hearts and its regulation by TFAP2

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  • Medientyp: E-Artikel
  • Titel: Characterization of TBX20 in human hearts and its regulation by TFAP2
  • Beteiligte: Hammer, Stefanie; Toenjes, Martje; Lange, Martin; Fischer, Jenny J.; Dunkel, Ilona; Mebus, Siegrun; Grimm, Christina H.; Hetzer, Roland; Berger, Felix; Sperling, Silke
  • Erschienen: Wiley, 2008
  • Erschienen in: Journal of Cellular Biochemistry
  • Sprache: Englisch
  • DOI: 10.1002/jcb.21686
  • ISSN: 0730-2312; 1097-4644
  • Entstehung:
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>The T‐box family of transcription factors has been shown to have major impact on human development and disease. In animal studies Tbx20 is essential for the development of the atrioventricular channel, the outflow tract and valves, suggesting its potential causative role for the development of Tetralogy of Fallot (TOF) in humans. In the presented study, we analyzed <jats:italic>TBX20</jats:italic> in cardiac biopsies derived from patients with TOF, ventricular septal defects (VSDs) and normal hearts. Mutation analysis did not reveal any disease causing sequence variation, however, <jats:italic>TBX20</jats:italic> is significantly upregulated in tissue samples of patients with TOF, but not VSD. In depth analysis of <jats:italic>TBX20</jats:italic> transcripts lead to the identification of two new exons 3′ to the known <jats:italic>TBX20</jats:italic> message resembling the mouse variant <jats:italic>Tbx20a</jats:italic>, as well as an extended 5′UTR. Functional analysis of the human <jats:italic>TBX20</jats:italic> promoter revealed a 100 bp region that contains strong activating elements. Within this core promoter region we recognized functional binding sites for TFAP2 transcription factors and identified TFAP2 as repressors of the <jats:italic>TBX20</jats:italic> gene in vitro and in vivo. Moreover, decreased <jats:italic>TFAP2C</jats:italic> levels in cardiac biopsies of TOF patients underline the biological significance of the pathway described. In summary, we provide first insights into the regulation of TBX20 and show its potential for human congenital heart diseases. J. Cell. Biochem. 104: 1022–1033, 2008. © 2008 Wiley‐Liss, Inc.</jats:p>