Abstract
We investigated the regulation of the activin/nodal-inducible distal element (DE) of the Xenopus goosecoid (gsc) promoter. On the basis of its interaction with the DE, we isolated a Xenopus homolog of the human Williams-Beuren syndrome critical region 11 (XWBSCR11), and further, show that it interacts with pathway-specific Smad2 and Smad3 in a ligand-dependent manner. Interestingly, we also find that XWBSCR11 functions cooperatively with FoxH1 (Fast-1) to stimulate DE-dependent transcription. We propose a mechanism in which FoxH1 functions together with Smads as a cofactor for the recruitment of transcription factors like XWBSCR11 in the process of activin/nodal-mediated gsc-specific induction. This mechanism provides considerable opportunities for modulation of transcription across a variety of activin/nodal-inducible genes, increasing diversity in promoter selection, thus leading to the differential induction of activin/nodal target genes.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activins / metabolism
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Amino Acid Sequence
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Animals
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Base Sequence
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Basic Helix-Loop-Helix Transcription Factors
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COS Cells
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Cloning, Molecular
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DNA-Binding Proteins / metabolism
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Helix-Loop-Helix Motifs
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Humans
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Ligands
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Models, Biological
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Molecular Sequence Data
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Promoter Regions, Genetic
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Protein Binding
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Protein Structure, Tertiary
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Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Amino Acid
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Signal Transduction
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Smad2 Protein
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Smad3 Protein
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Trans-Activators / metabolism
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Transcription Factors / chemistry*
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Transcription Factors / physiology*
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Transcription, Genetic
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Williams Syndrome / metabolism*
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Xenopus
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Xenopus Proteins / chemistry*
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Xenopus Proteins / physiology*
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Ligands
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Proteins
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SMAD2 protein, human
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SMAD3 protein, human
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Smad2 Protein
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Smad2 protein, Xenopus
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Smad3 Protein
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Trans-Activators
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Transcription Factors
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WBSCR11 protein, Xenopus
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Xenopus Proteins
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madh3 protein, Xenopus
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Activins