Applications of high-throughput reporter assays to gene regulation studies

Determining the rules of transcriptional regulation, associated with a complex transcription factor grammar, is fundamental to understand the control of most biological processes, disease mechanisms, and evolution. High-throughput reporter assays, such as MPRAs and STARR-seq, have enabled systematic functional annotations of genomes and have provided large substrates for training machine learning models to determine these rules, predict the activity of native and synthetic elements, and design elements for different applications. This review provides an overview of high-throughput reporter assays and their applications for the study of enhancers, promoters, silencers and insulators. We discuss how these assays help identify causal disease-associated non-coding variants and design synthetic elements with desired features for functional studies or therapeutic purposes.