The role of a Williams-Beuren syndrome-associated helix-loop-helix domain-containing transcription factor in activin/nodal signaling.
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.
Ring
Colleen
C
Department of Developmental and Cell Biology, and Developmental Biology Center, University of California, Irvine, California 92697-2300, USA.
Ogata
Souichi
S
Meek
Lauren
L
Song
Jihwan
J
Ohta
Tatsuru
T
Miyazono
Kohei
K
Cho
Ken W Y
KW
D028341:Activins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D019556:COS Cells; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology*; D014158:Transcription, Genetic; D018980:Williams Syndrome / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000737:chemistry* / Q000502:physiology*
D028341:Activins; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D008024:Ligands; D011506:Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497785:Smad2 protein, Xenopus; C454114:WBSCR11 protein, Xenopus; C497789:madh3 protein, Xenopus