The role of a Williams-Beuren syndrome-associated helix-loop-helix domain-containing transcription factor in activin/nodal signaling

Genes Dev. 2002 Apr 1;16(7):820-35. doi: 10.1101/gad.963802.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activins / metabolism
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors
  • COS Cells
  • Cloning, Molecular
  • DNA-Binding Proteins / metabolism
  • Helix-Loop-Helix Motifs
  • Humans
  • Ligands
  • Models, Biological
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Structure, Tertiary
  • Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Smad2 Protein
  • Smad3 Protein
  • Trans-Activators / metabolism
  • Transcription Factors / chemistry*
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Williams Syndrome / metabolism*
  • Xenopus
  • Xenopus Proteins / chemistry*
  • Xenopus Proteins / physiology*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Ligands
  • Proteins
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad2 protein, Xenopus
  • Smad3 Protein
  • Trans-Activators
  • Transcription Factors
  • WBSCR11 protein, Xenopus
  • Xenopus Proteins
  • madh3 protein, Xenopus
  • Activins