PMID:14550786

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
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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

References

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