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Rembold, M., Ciglar, L., Yáñez-Cuna, J.O., Zinzen, R.P., Girardot, C., Jain, A., Welte, M.A., Stark, A., Leptin, M., Furlong, E.E. (2014). A conserved role for Snail as a potentiator of active transcription.  Genes Dev. 28(2): 167--181.
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Research paper

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.

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PMC3909790 (PMC) (EuropePMC)
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Personal communication to FlyBase

Furlong Lab EMBL TFBS contribution.
Monfort and Furlong, 2015.1.15, Furlong Lab EMBL TFBS contribution. [FBrf0227761]

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    Genes Dev.
    Genes & Development
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