The selection and function of cell type-specific enhancers

Enhancers are genetic elements that have major roles in determining cell type-specific gene expression patterns and responses to internal and external signals.Mammalian genomes contain millions of enhancers, but only a subset of them are selected and activated in each cell type in the body.Enhancer selection involves collaborative interactions between 'pioneer' or lineage-determining transcription factors. Such factors are able to prime enhancers in a cell type-specific manner by binding to closely spaced recognition motifs.Signal-dependent transcription factors, such as nuclear receptors and nuclear factor-κB (NF-κB), primarily bind to regions of the genome that are primed in a cell type-specific manner by lineage-determining transcription factors. This enables such broadly expressed, signal-dependent transcription factors to regulate gene expression in a cell type-specific manner.A proportion of the genome contains a very high density of marks of active enhancers. Such enhancer-rich genomic regions, which are called super-enhancers, are different in each cell type and regulate genes required for establishing cell identity and function.An understanding of the mechanisms underlying the cell type-specific selection and function of enhancers will improve our understanding of the effects of natural genetic variation on complex phenotypes and diseases.