Regulation of the Lim-1 gene is mediated through conserved FAST-1/FoxH1 sites in the first intron.

The Lim-1 gene encodes a LIM-homeodomain transcription factor that is highly conserved among vertebrates and is required for successful gastrulation and head formation. The expression of this gene in the mesoderm of the gastrula is known to require an activin/nodal signal. Earlier studies have shown that the Xenopus Lim-1 (Xlim-1) gene contains an activin response element (ARE) in its first intron, which cooperates with an activin-unresponsive upstream promoter in the regulation of the gene. Here, we show that the Xlim-1 ARE contains a cluster of FAST-1/FoxH1 and Smad4 recognition sites; such sites have been shown to mediate activin/nodal responses in other genes. By using reporter constructs with mutated FAST-1/FoxH1 sites and FAST-1/FoxH1 protein chimeras, we show that the regulation of Xlim-1 by activin depends on FAST-1/FoxH1 function. Comparative studies on the zebrafish lim1 gene indicate the presence of FoxH1 sites in the first intron of this gene and provide evidence for the requirement for FoxH1 function in its regulation. These results illuminate the conserved nature of the transcriptional regulation of the Lim-1 gene in different vertebrate animals.