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

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

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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]

Original language	English
Pages (from-to)	3949-3961
Journal	Cellular and Molecular Life Sciences
Volume	68
Issue number	23
DOIs	https://doi.org/10.1007/s00018-011-0693-7
Publication status	Published - 2011

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Cite this

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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",

note = "Reporting year: 2011 Metis note: 3214269;",

year = "2011",

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

language = "English",

volume = "68",

pages = "3949--3961",

journal = "Cellular and Molecular Life Sciences",

issn = "1420-682X",

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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 -

Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43

Abstract

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