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PMID:17584735

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Citation

Farin, HF, Bussen, M, Schmidt, MK, Singh, MK, Schuster-Gossler, K and Kispert, A (2007) Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors. J. Biol. Chem. 282:25748-59

Abstract

Tbox18 (Tbx18) and Tbox15 (Tbx15) encode a closely related pair of vertebrate-specific T-box (Tbx) transcription factors. Functional analyses in the mouse have proven the requirement of Tbx15 in skin and skeletal development and of Tbx18 in the formation of the vertebral column, the ureter, and the posterior pole of the heart. Despite the accumulation of genetic data concerning the embryological roles of these genes, it is currently unclear how Tbx18 and Tbx15 exert their function on the molecular level. Here, we have initiated a molecular analysis of Tbx18 and Tbx15 proteins and have characterized functional domains for nuclear localization, DNA binding, and transcriptional modulation. We show that both proteins homo- and heterodimerize, bind to various combinations of T half-sites, and repress transcription in a Groucho-dependent manner. Competition with activating T-box proteins may constitute one mode of action as we show that Tbx18 interacts with Gata4 and Nkx2-5 and competes Tbx5-mediated activation of the cardiac Natriuretic peptide precursor type a-promoter and that ectopic expression of Tbx18 down-regulates Tbx6-activated Delta-like 1 expression in the somitic mesoderm in vivo.

Links

PubMed Online version:10.1074/jbc.M703724200

Keywords

Active Transport, Cell Nucleus/physiology; Animals; Atrial Natriuretic Factor/genetics; Atrial Natriuretic Factor/metabolism; Cell Nucleus/metabolism; Dimerization; GATA4 Transcription Factor/genetics; GATA4 Transcription Factor/metabolism; Gene Expression Regulation, Developmental/physiology; HeLa Cells; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Humans; Intercellular Signaling Peptides and Proteins/genetics; Intercellular Signaling Peptides and Proteins/metabolism; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mesoderm/metabolism; Mice; Natriuretic Peptide, C-Type/genetics; Natriuretic Peptide, C-Type/metabolism; Protein Binding/physiology; Protein Precursors/genetics; Protein Precursors/metabolism; Protein Structure, Tertiary/physiology; Repressor Proteins/genetics; Repressor Proteins/metabolism; Response Elements/physiology; Skin/embryology; Somites/metabolism; T-Box Domain Proteins/genetics; T-Box Domain Proteins/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic/physiology

Significance

Annotations

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

MOUSE:TBX15

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:TBX15

enables

GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0001952)

Seeded From UniProt

complete

MOUSE:TBX15

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9EPZ6

F

Seeded From UniProt

complete

MOUSE:TBX15

part_of

GO:0090571: RNA polymerase II transcription repressor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TBX15

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TBX15

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TBX15

enables

GO:0000976: transcription cis-regulatory region binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TBX15

enables

GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TBX15

enables

GO:0042803: protein homodimerization activity

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O70306

F

Seeded From UniProt

complete

MOUSE:NKX25

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9EPZ6

F

Seeded From UniProt

complete

MOUSE:GATA4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9EPZ6

F

Seeded From UniProt

complete

MOUSE:TBX18

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TBX18

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:TBX18

enables

GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0001952)

Seeded From UniProt

complete

MOUSE:TBX18

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O70306

F

Seeded From UniProt

complete

MOUSE:TBX18

part_of

GO:0090571: RNA polymerase II transcription repressor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TBX18

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TBX18

enables

GO:0000976: transcription cis-regulatory region binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TBX18

enables

GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TBX18

enables

GO:0042803: protein homodimerization activity

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9EPZ6

F

Seeded From UniProt

complete

MOUSE:TBX18

involved_in

GO:0060829: negative regulation of canonical Wnt signaling pathway involved in neural plate anterior/posterior pattern formation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TBX18

enables

GO:0061629: RNA polymerase II-specific DNA-binding transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P42582

F

Seeded From UniProt

complete

MOUSE:TBX18

enables

GO:0061629: RNA polymerase II-specific DNA-binding transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q08369

F

Seeded From UniProt

complete

See also

References

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