• C.J. Boogerd
  • L.Y. Wong
  • M. van den Boogaard
  • M.A.J. Bakker
  • F. Tessadori
  • J. Bakkers
  • P.A.C. 't Hoen
  • A.F. Moorman
  • V.M. Christoffels
  • P. Barnett
Tbx3, a T-box transcription factor, regulates key steps in development of the heart and other organ systems. Here, we identify Sox4 as an interacting partner of Tbx3. Pull-down and nuclear retention assays verify this interaction and in situ hybridization reveals Tbx3 and Sox4 to co-localize extensively in the embryo including the atrioventricular and outflow tract cushion mesenchyme and a small area of interventricular myocardium. Tbx3, SOX4, and SOX2 ChIP data, identify a region in intron 1 of Gja1 bound by all tree proteins and subsequent ChIP experiments verify that this sequence is bound, in vivo, in the developing heart. In a luciferase reporter assay, this element displays a synergistic antagonistic response to co-transfection of Tbx3 and Sox4 and in vivo, in zebrafish, drives expression of a reporter in the heart, confirming its function as a cardiac enhancer. Mechanistically, we postulate that Sox4 is a mediator of Tbx3 transcriptional activity. [KEYWORDS: Amino Acid Sequence; Animals; COS Cells; Cercopithecus aethiops; Connexin 43/ genetics; Gene Expression Regulation; Humans; Male; Mice; Molecular Sequence Data; SOXC Transcription Factors/chemistry/ metabolism; T-Box Domain Proteins/ metabolism; Transcription, Genetic; Zebrafish]
Original languageEnglish
Pages (from-to)3949-3961
JournalCellular and Molecular Life Sciences
Issue number23
StatePublished - 2011

ID: 122460