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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.
FlyBase ID
FBrf0223915
Publication Type
Research paper
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.
PubMed ID
PubMed Central ID
PMC3909790 (PMC) (EuropePMC)
Related Publication(s)
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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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Genes Dev.
    Title
    Genes & Development
    Publication Year
    1987-
    ISBN/ISSN
    0890-9369
    Data From Reference