A conserved role for Snail as a potentiator of active transcription

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.M.

A conserved role for Snail as a potentiator of active transcription

Tools

PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB

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
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

Repository Staff Only: item control page

Download Statistics

Downloads

Downloads per month over past year