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A conserved role for Snail as a potentiator of active transcription

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Item Type:Article
Title:A conserved role for Snail as a potentiator of active transcription
Creators Name:Rembold, M., Ciglar, L., Yáñez-Cuna, J.O., Zinzen, R.P., Girardot, C., Jain, A., Welte, M.A., Stark, A., 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
Publisher:Cold Spring Harbor Laboratory Press
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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