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PMID:14550786

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Citation

Stennard, FA, Costa, MW, Elliott, DA, Rankin, S, Haast, SJ, Lai, D, McDonald, LP, Niederreither, K, Dolle, P, Bruneau, BG, Zorn, AM and Harvey, RP (2003) Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart. Dev. Biol. 262:206-24

Abstract

Tbx20 is a member of the T-box transcription factor family expressed in the forming hearts of vertebrate and invertebrate embryos. We report here analysis of Tbx20 expression during murine cardiac development and assessment of DNA-binding and transcriptional properties of Tbx20 isoforms. Tbx20 was expressed in myocardium and endocardium, including high levels in endocardial cushions. cDNAs generated by alternative splicing encode at least four Tbx20 isoforms, and Tbx20a uniquely carried strong transactivation and transrepression domains in its C terminus. Isoforms with an intact T-box bound specifically to DNA sites resembling the consensus brachyury half site, although with less avidity compared with the related factor, Tbx5. Tbx20 physically interacted with cardiac transcription factors Nkx2-5, GATA4, and GATA5, collaborating to synergistically activate cardiac gene expression. Among cardiac GATA factors, there was preferential synergy with GATA5, implicated in endocardial differentiation. In Xenopus embryos, enforced expression of Tbx20a, but not Tbx20b, led to induction of mesodermal and endodermal lineage markers as well as cell migration, indicating that the long Tbx20a isoform uniquely bears functional domains that can alter gene expression and developmental behaviour in an in vivo context. We propose that Tbx20 plays an integrated role in the ancient myogenic program of the heart, and has been additionally coopted during evolution of vertebrates for endocardial cushion development.

Links

PubMed

Keywords

Alternative Splicing; Animals; DNA/metabolism; DNA-Binding Proteins/metabolism; GATA4 Transcription Factor; GATA5 Transcription Factor; Gene Expression Regulation, Developmental/physiology; Heart/embryology; Homeodomain Proteins/metabolism; Mice; Mutation; Protein Isoforms; T-Box Domain Proteins/genetics; T-Box Domain Proteins/metabolism; Transcription Factors/metabolism; Xenopus; Xenopus Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:NKX25

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9ES03

F

Seeded From UniProt

complete

MOUSE:NKX25

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TBX5

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TBX5

enables

GO:0000977: RNA polymerase II transcription regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:GATA5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9ES03

F

Seeded From UniProt

complete

MOUSE:GATA4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9ES03

F

Seeded From UniProt

complete

MOUSE:TBX20

enables

GO:0000978: RNA polymerase II cis-regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TBX20

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0001952)

Seeded From UniProt

complete

MOUSE:TBX20

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TBX20

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TBX20

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TBX20

enables

GO:0000977: RNA polymerase II transcription regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TBX20

enables

GO:0000981: DNA-binding transcription factor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TBX20

enables

GO:0001085: RNA polymerase II transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P97489

F

Seeded From UniProt

complete

MOUSE:TBX20

enables

GO:0001085: RNA polymerase II transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q08369

F

Seeded From UniProt

complete

MOUSE:TBX20

enables

GO:0001102: RNA polymerase II activating transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P42582

F

Seeded From UniProt

complete

XENLA:TBX20

involved_in

GO:0000578: embryonic axis specification

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

XENLA:TBX20

involved_in

GO:0001706: endoderm formation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

XENLA:TBX20

involved_in

GO:0048370: lateral mesoderm formation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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