Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43

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

doi:10.1007/s00018-011-0693-7

Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43

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

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

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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]

Originele taal-2	Engels
Pagina's (van-tot)	3949-3961
Tijdschrift	Cellular and Molecular Life Sciences
Volume	68
Nummer van het tijdschrift	23
DOI's	https://doi.org/10.1007/s00018-011-0693-7
Status	Gepubliceerd - 2011

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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. [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]",

author = "C.J. Boogerd and L.Y. Wong and {van den Boogaard}, M. and M.A.J. Bakker and F. Tessadori and J. Bakkers and {'t Hoen}, P.A.C. and A.F. Moorman and V.M. Christoffels and P. Barnett",

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doi = "10.1007/s00018-011-0693-7",

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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

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VL - 68

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EP - 3961

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

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ER -

Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43

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