Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43

TY - JOUR

T1 - Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43

AU - Boogerd, C.J.

AU - Wong, L.Y.

AU - van den Boogaard, M.

AU - Bakker, M.A.J.

AU - Tessadori, F.

AU - Bakkers, J.

AU - 't Hoen, P.A.C.

AU - Moorman, A.F.

AU - Christoffels, V.M.

AU - Barnett, P.

N1 - Reporting year: 2011 Metis note: 3214269;

PY - 2011

Y1 - 2011

N2 - 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]

AB - 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]

U2 - 10.1007/s00018-011-0693-7

DO - 10.1007/s00018-011-0693-7

M3 - Article

SN - 1420-682X

VL - 68

SP - 3949

EP - 3961

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

IS - 23

ER -