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

2002; Cold Spring Harbor Laboratory Press; Volume: 16; Issue: 7 Linguagem: Inglês

10.1101/gad.963802

1549-5477

Colleen Ring, Souichi Ogata, Lauren M. Meek, Jihwan Song, Tatsuru Ohta, Kohei Miyazono, Ken W.Y. Cho,

Cancer-related gene regulation

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.