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PMID:11071761

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Citation

Dai, H, Hogan, C, Gopalakrishnan, B, Torres-Vazquez, J, Nguyen, M, Park, S, Raftery, LA, Warrior, R and Arora, K (2000) The zinc finger protein schnurri acts as a Smad partner in mediating the transcriptional response to decapentaplegic. Dev. Biol. 227:373-87

Abstract

In Drosophila, a BMP-related ligand Decapentaplegic (Dpp) is essential for cell fate specification during embryogenesis and in imaginal disc development. Dpp signaling culminates in the phosphorylation and nuclear translocation of Mothers against dpp (Mad), a receptor-specific Smad that can bind DNA and regulate the transcription of Dpp-responsive genes. Genetic analysis has implicated Schnurri (Shn), a zinc finger protein that shares homology with mammalian transcription factors, in the Dpp signal transduction pathway. However, a direct role for Shn in regulating the transcriptional response to Dpp has not been demonstrated. In this study we show that Shn acts as a DNA-binding Mad cofactor in the nuclear response to Dpp. Shn can bind DNA in a sequence-specific manner and recognizes sites within a well-characterized Dpp-responsive promoter element, the B enhancer of the Ultrabithorax (Ubx) gene. The Shn-binding sites are relevant for in vivo expression, since mutations in these sites affect the ability of the enhancer to respond to Dpp. Furthermore we find that Shn and Mad can interact directly through discrete domains. To examine the relative contribution of the two proteins in the regulation of endogenous Dpp target genes we developed a cell culture assay and show that Shn and Mad act synergistically to induce transcription. Our results suggest that cooperative interactions between these two transcription factors could play an important role in the regulation of Dpp target genes. This is the first evidence that Dpp/BMP signaling in flies requires the direct interaction of Mad with a partner transcription factor.

Links

PubMed Online version:10.1006/dbio.2000.9901

Keywords

Animals; Animals, Genetically Modified; Base Sequence; Binding Sites/genetics; COS Cells; Cells, Cultured; DNA/genetics; DNA/metabolism; DNA Primers/genetics; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Digestive System/embryology; Digestive System/metabolism; Drosophila/embryology; Drosophila/genetics; Drosophila/metabolism; Drosophila Proteins; Enhancer Elements, Genetic; Genes, Insect; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Insect Proteins/genetics; Insect Proteins/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Transcriptional Activation; Two-Hybrid System Techniques; Zinc Fingers

Significance

Annotations

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

DROME:A0A0B4KFC0

involved_in

GO:0030509: BMP signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:A0A0B4KFC0

involved_in

GO:0030509: BMP signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:A0A0B4KFC0

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:A0A0B4KFC0

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

DROME:A0A0B4KFC0

enables

GO:0003713: transcription coactivator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:A0A0B4KFC0

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

DROME:A0A0B4KFC0

enables

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

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0011648

F

Seeded From UniProt

complete

DROME:O62609

involved_in

GO:0030509: BMP signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:O62609

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

DROME:MAD

involved_in

GO:0030509: BMP signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:MAD

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

DROME:MAD

enables

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

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0003396

F

Seeded From UniProt

complete

DROME:Q9VMT1

involved_in

GO:0030509: BMP signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:MAD

enables

GO:0001102: RNA polymerase II activating transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0003396

F

Seeded From UniProt

complete

DROME:MAD

enables

GO:0003713: transcription coactivator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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