Laminin is a major component of the extracellular matrix. The laminin ␥1 chain is the least variant component of the laminin heterotrimeric assembly. The laminin ␥1 chain gene (LAMC1) expression is induced by several factors, including transforming growth factor-␤ (TGF-␤). LAMC1 promoter contains a highly conserved transcriptional element, bcn-1. We screened cDNA libraries with the yeast one-hybrid system to identify transcriptional factors that are recognized by the bcn-1 motif. Using this

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... tegy we isolated the basic helixloop-helix/leucine zipper (bHLHzip) E-box-binding transcription factor, TFE3. Until now, the E-box was the only element known to recruit the bHLHzip transcription factors. Although the bcn-1 element only remotely resembles the E-box sequence, we show that TFE3 binds and activates the bcn-1 element. TFE3 cooperates with Smad proteins in the activation of the LAMC1 promoter in cells, an effect that is critically dependent not only on the bcn-1 element but also on one of the Smad-binding elements (SBE). The cooperative induction of the LAMC1 promoter and the endogenous LAMC1 gene by TFE3 and Smad3 is augmented by the TGF-␤ signaling pathway. Thus, the bcn-1 is a novel TFE3-dependent TGF-␤ target element that regulates LAMC1 gene expression.