Universität zu Köln

Rembold, Martina, Ciglar, Lucia, Yanez-Cuna, J. Omar, Zinzen, Robert P., Girardot, Charles ORCID: 0000-0003-4301-3920, Jain, Ankit ORCID: 0000-0003-4032-1442, Welte, Michael A., Stark, Alexander ORCID: 0000-0003-2611-0841, Leptin, Maria ORCID: 0000-0001-7097-348X and Furlong, Eileen E. M. (2014). A conserved role for Snail as a potentiator of active transcription. Genes Dev., 28 (2). S. 167 - 182. COLD SPRING HARBOR: COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT. ISSN 1549-5477

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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 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rembold, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Ciglar, Lucia UNSPECIFIED UNSPECIFIED UNSPECIFIED Yanez-Cuna, J. Omar UNSPECIFIED UNSPECIFIED UNSPECIFIED Zinzen, Robert P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Girardot, Charles UNSPECIFIED orcid.org/0000-0003-4301-3920 UNSPECIFIED Jain, Ankit UNSPECIFIED orcid.org/0000-0003-4032-1442 UNSPECIFIED Welte, Michael A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stark, Alexander UNSPECIFIED orcid.org/0000-0003-2611-0841 UNSPECIFIED Leptin, Maria UNSPECIFIED orcid.org/0000-0001-7097-348X UNSPECIFIED Furlong, Eileen E. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-448484
DOI:	10.1101/gad.230953.113
Journal or Publication Title:	Genes Dev.
Volume:	28
Number:	2
Page Range:	S. 167 - 182
Date:	2014
Publisher:	COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
Place of Publication:	COLD SPRING HARBOR
ISSN:	1549-5477
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPITHELIAL-MESENCHYMAL TRANSITION; EARLY MESODERM DEVELOPMENT; SHORT-RANGE REPRESSION; CELL-SHAPE CHANGES; DROSOPHILA-EMBRYO; GENE-EXPRESSION; DORSOVENTRAL PATTERN; NUCLEAR-LOCALIZATION; REGULATORY CODE; DIRECT TARGET Multiple languages Cell Biology; Developmental Biology; Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/44848