title: 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.
authors.affiliation: Heart Failure Research Centre, Academic Medical Centre, University of Amsterdam, The Netherlands.
authors.forename: C J J
authors.initials: CJ
authors.lastname: Boogerd
authors.forename: L Y E
authors.initials: LY
authors.lastname: Wong
authors.forename: M
authors.initials: M
authors.lastname: van den Boogaard
authors.forename: M L
authors.initials: ML
authors.lastname: Bakker
authors.forename: F
authors.initials: F
authors.lastname: Tessadori
authors.forename: J
authors.initials: J
authors.lastname: Bakkers
authors.forename: P A C
authors.initials: PA
authors.lastname: 't Hoen
authors.forename: A F
authors.initials: AF
authors.lastname: Moorman
authors.forename: V M
authors.initials: VM
authors.lastname: Christoffels
authors.forename: P
authors.initials: P
authors.lastname: Barnett
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D018031:Connexin 43 / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D055751:SOXC Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D015027:Zebrafish
chemical_list: D018031:Connexin 43; D055751:SOXC Transcription Factors; C489990:Sox4 protein, mouse; D020825:T-Box Domain Proteins; C106884:TBX3 protein, human; C491460:Tbx3 protein, mouse