Transcriptional Enhancers inDrosophila

Abstract

Key discoveries in Drosophila have shaped our understanding of cellular “enhancers.” With a special focus on the fly, this chapter surveys properties of these adaptable cis-regulatory elements, whose actions are critical for the complex spatial/temporal transcriptional regulation of gene expression in metazoa. The powerful combination of genetics, molecular biology, and genomics available in Drosophila has provided an arena in which the developmental role of enhancers can be explored. Enhancers are characterized by diverse low- or high-throughput assays, which are challenging to interpret, as not all of these methods of identifying enhancers produce concordant results. As a model metazoan, the fly offers important advantages to comprehensive analysis of the central functions that enhancers play in gene expression, and their critical role in mediating the production of phenotypes from genotype and environmental inputs. A major challenge moving forward will be obtaining a quantitative understanding of how these cis-regulatory elements operate in development and disease.

Filtering the Junk: Assigning Function to the Mosquito Non-Coding Genome

“…The process for discovering eRNAs generally includes two steps, the use of an indirect CRE discovery method, such as ChIP-seq, coupled with RNA-seq. Nothing is known about eRNAs in mosquitoes, but they likely play an important role in the regulation of gene expression in Drosophila [ 146 ].…”

Repression precedes the stepwise evolution of a highly specific gene expression pattern

“…The generation of highly-specific gene expression patterns is often due to the combinatorial actions of activators and repressors that form a modular enhancer driving these expression patterns (1, 4). However, the evolutionary history that leads to the origin of these enhancers is not always clear.…”

“…Highly-specific gene expression patterns are central to the development and evolution of multicellular organisms. These expression patterns are controlled by the action of modular cis -regulatory elements called enhancers (1). Enhancers are generally made of positive regulatory elements, such as activator sequences that recruit transcriptional activators to drive expression of a gene, and negative regulatory elements, such as repressor sequences that recruit transcriptional repressors to inhibit gene expression (1–3).…”

“…These expression patterns are controlled by the action of modular cis -regulatory elements called enhancers (1). Enhancers are generally made of positive regulatory elements, such as activator sequences that recruit transcriptional activators to drive expression of a gene, and negative regulatory elements, such as repressor sequences that recruit transcriptional repressors to inhibit gene expression (1–3). The overlapping and combinatorial actions of activators and repressors within an enhancer control highly-specific gene expression in time and space (4).…”

“…A well-studied example of this logic is the even-skipped ( eve ) stripe 2 enhancer, where the combinatorial actions of two activators and three repressors define a single stripe of eve expression in the developing insect embryo (1,5–7). In the past few decades, numerous studies have demonstrated that changes in enhancer activities can lead to novel expression patterns and evolutionary innovations in morphology and physiology (8–10).…”