Enhancers: A Focus on Synthetic Biology and Correlated Gene Expression

Enhancers are central for the regulation of metazoan transcription but have proven difficult to study, primarily due to a myriad of interdependent variables shaping their activity. Consequently, synthetic biology has emerged as the main approach for dissecting mechanisms of enhancer function. We start by reviewing simple but highly parallel reporter assays, which have been successful in quantifying the complexity of the activator/coactivator mechanisms at enhancers. We then describe studies that examine how enhancers function in the genomic context and in combination with other enhancers, revealing that they activate genes through a variety of different mechanisms, working together as a system. Here, we primarily focus on synthetic reporter genes that can quantify the dynamics of enhancer biology through time. We end by considering the consequences of having many genes and enhancers within a 'local environment', which we believe leads to correlated gene expression and likely reports on the general principles of enhancer biology.