A conserved role for Snail as a potentiator of active transcription

作者：Rembold Martina; Ciglar Lucia; Yanez Cuna J Omar; Zinzen Robert P; Girardot Charles; Jain Ankit; Welte Michael A; Stark Alexander; Leptin Maria^*; Furlong Eileen E M

来源：Genes & Development, 2014, 28(2): 167-181.

DOI：10.1101/gad.230953.113

• transcription factor
• Snail
• Twist
• repression
• activation
• spatiotemporal gene expression
• Drosophila embryogenesis

The transcription factors of the Snail family are key regulators of epithelial-mesenchymal transitions, cell morphogenesis, and tumor metastasis. Since its discovery in Drosophila similar to 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.

• 出版日期2014-1-15