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The Regulatory Genome
Multicellular organisms contain a variety of cell types that are morphologically and functionally distinct even though they typically contain the same genomic DNA. Differences stem from differential gene expression. Gene regulatory genomic regions (enhancers) are well studied, yet despite major efforts, such as Encode and modEncode, the number of enhancers in animal genomes and their genomic positions, cell-type specificity, and strengths are largely unknown. Arnold et al. (p. 1074, published online 17 January) report a method, termed STARR-seq, that measures the strength of enhancers genome-wide, giving insight into the organization of the regulatory genome.
Abstract
Genomic enhancers are important regulators of gene expression, but their identification is a challenge, and methods depend on indirect measures of activity. We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes. When applied to the Drosophila genome, STARR-seq identifies thousands of cell type–specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map. This map reveals the highly complex regulation of transcription, with several independent enhancers for both developmental regulators and ubiquitously expressed genes. STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans.
