Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43

• Published in: Cellular and molecular life sciences : CMLS Vol. 68; no. 23; pp. 3949 - 3961
• Main Authors: Boogerd, C. J. J., Wong, L. Y. E., van den Boogaard, M., Bakker, M. L., Tessadori, F., Bakkers, J., ‘t Hoen, P. A. C., Moorman, A. F., Christoffels, V. M., Barnett, P.
• Format: Journal Article
• Language: English
• Published: Basel SP Birkhäuser Verlag Basel 01-12-2011; Springer Nature B.V
• Subjects: Amino Acid Sequence; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Chlorocebus aethiops; Connexin 43 - genetics; COS Cells; Danio rerio; Embryos; Freshwater; Gene Expression Regulation; Humans; Hybridization; Life Sciences; Male; Mice; Molecular Sequence Data; Proteins; Research Article; SOXC Transcription Factors - chemistry; SOXC Transcription Factors - metabolism; T-Box Domain Proteins - metabolism; Transcription, Genetic; Zebrafish; Gja1; Enhancer; Heart development; Interaction; Tbx3; Sox4
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-011-0693-7

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.