Characterization of TBX20 in human hearts and its regulation by TFAP2.

Abstract:

: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 TBX20 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, TBX20 is significantly upregulated in tissue samples of patients with TOF, but not VSD. In depth analysis of TBX20 transcripts lead to the identification of two new exons 3' to the known TBX20 message resembling the mouse variant Tbx20a, as well as an extended 5'UTR. Functional analysis of the human TBX20 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 TBX20 gene in vitro and in vivo. Moreover, decreased TFAP2C 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.

journal_name

J Cell Biochem

authors

Hammer S,Toenjes M,Lange M,Fischer JJ,Dunkel I,Mebus S,Grimm CH,Hetzer R,Berger F,Sperling S

doi

10.1002/jcb.21686

subject

Has Abstract

pub_date

2008-06-01 00:00:00

pages

1022-33

issue

3

eissn

0730-2312

issn

1097-4644

journal_volume

104

pub_type

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