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Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43.


ABSTRACT: 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.

SUBMITTER: Boogerd CJ 

PROVIDER: S-EPMC3214269 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43.

Boogerd C J J CJ   Wong L Y E LY   van den Boogaard M M   Bakker M L ML   Tessadori F F   Bakkers J J   't Hoen P A C PA   Moorman A F AF   Christoffels V M VM   Barnett P P  

Cellular and molecular life sciences : CMLS 20110503 23


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  ...[more]

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