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Genes Dev February 15, 2000; 14 (4): 435-51.
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Homeodomain and winged-helix transcription factors recruit activated Smads to distinct promoter elements via a common Smad interaction motif.

Germain S , Howell M , Esslemont GM , Hill CS .

We have investigated the regulation of the activin-inducible distal element (DE) of the Xenopus goosecoid promoter. The results show that paired-like homeodomain transcription factors of the Mix family, Mixer and Milk, but not Mix.1, mediate activin/TGF-beta-induced transcription through the DE by interacting with the effector domain of Smad2, thereby recruiting active Smad2/Smad4 complexes to the Mixer/Milk-binding site. We identify a short motif in the carboxyl termini of Mixer and Milk, which is demonstrated to be both necessary and sufficient for interaction with the effector domain of Smad2 and is required for mediating activin/TGF-beta-induced transcription. This motif is not confined to these homeodomain proteins, but is also present in the Smad2-interacting winged-helix proteins Xenopus Fast-1, human Fast-1, and mouse Fast-2. We demonstrate directly that transcription factors of different DNA-binding specificity recruit activated Smads to distinct promoter elements via a common mechanism. These observations, together with the temporal and spatial expression patterns of Mixer and Milk, lead us to propose a model for mesoendoderm formation in Xenopus in which these homeodomain transcription factor/Smad complexes play a role in initiating and maintaining transcription of target genes in response to endogenous activin-like signals.

PubMed ID: 10691736
PMC ID: PMC316385
Article link: Genes Dev

Species referenced: Xenopus laevis
Genes referenced: bix1.1 bix1.2 cat.2 cer1 foxh1 gdf1 gsc inhba mix1 mixer myc smad2 smad4 smad4.2 tbx2 vegt
Antibodies: Smad2 Ab6

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References [+] :
Blumberg, Organizer-specific homeobox genes in Xenopus laevis embryos. 1991, Pubmed, Xenbase