TitleTranscriptional repression via antilooping in the Drosophila embryo.
Publication TypeJournal Article
Year of Publication2012
AuthorsChopra, VS, Kong, N, Levine, M
JournalProc Natl Acad Sci U S A
Volume109
Issue24
Pagination9460-4
Date Published2012 Jun 12
KeywordsAnimals, Drosophila, Enhancer Elements, Genetic, Polymerase Chain Reaction, Promoter Regions, Genetic, Repressor Proteins, Transcription, Genetic
Abstract

Transcriptional repressors are thought to inhibit gene expression by interfering with the binding or function of RNA Polymerase II, perhaps by promoting local chromatin condensation. Here, we present evidence for a distinctive mechanism of repression, whereby sequence-specific repressors prevent the looping of distal enhancers to the promoter. Particular efforts focus on the Snail repressor, which plays a conserved role in promoting epithelial-mesenchyme transitions in both invertebrates and vertebrates, including mesoderm invagination in Drosophila, neural crest migration in vertebrates, and tumorigenesis in mammals. Chromosome conformation capture experiments were used to examine enhancer looping at Snail target genes in wild-type and mutant embryos. These studies suggest that the Snail repressor blocks the formation of fruitful enhancer-promoter interactions when bound to a distal enhancer. This higher-order mechanism of transcriptional repression has broad implications for the control of gene activity in metazoan development.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.