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| Item Type: | Article |
|---|---|
| Title: | A conserved role for Snail as a potentiator of active transcription |
| Creators Name: | Rembold, M. and Ciglar, L. and Yáñez-Cuna, J.O. and Zinzen, R.P. and Girardot, C. and Jain, A. and Welte, M.A. and Stark, A. and Leptin, M. and Furlong, E.E.M. |
| Abstract: | The transcription factors of the Snail family are key regulators of epithelial-mesenchymal transitions, cell morphogenesis, and tumor metastasis. Since its discovery in Drosophila ~25 years ago, Snail has been extensively studied for its role as a transcriptional repressor. Here we demonstrate that Drosophila Snail can positively modulate transcriptional activation. By combining information on in vivo occupancy with expression profiling of hand-selected, staged snail mutant embryos, we identified 106 genes that are potentially directly regulated by Snail during mesoderm development. In addition to the expected Snail-repressed genes, almost 50% of Snail targets showed an unanticipated activation. The majority of "Snail-activated" genes have enhancer elements cobound by Twist and are expressed in the mesoderm at the stages of Snail occupancy. Snail can potentiate Twist-mediated enhancer activation in vitro and is essential for enhancer activity in vivo. Using a machine learning approach, we show that differentially enriched motifs are sufficient to predict Snail's regulatory response. In silico mutagenesis revealed a likely causative motif, which we demonstrate is essential for enhancer activation. Taken together, these data indicate that Snail can potentiate enhancer activation by collaborating with different activators, providing a new mechanism by which Snail regulates development. |
| Keywords: | Transcription Factor, Snail, Twist, Repression, Activation, Spatiotemporal Gene Expression, Drosophila Embryogenesis, Animals, Drosophila |
| Source: | Genes & Development |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Volume: | 28 |
| Number: | 2 |
| Page Range: | 167-181 |
| Date: | 15 January 2014 |
| Official Publication: | https://doi.org/10.1101/gad.230953.113 |
| PubMed: | View item in PubMed |
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