Actors with Multiple Roles: Pleiotropic Enhancers and the Paradigm of Enhancer Modularity

Recent genome-wide and locus-specific functional studies uncovered that enhancer pleiotropy is pervasive in gene regulatory regions of animal genomes. Transcription factor binding sites within pleiotropic enhancers can be reused in different contexts, implying that binding sites can be pleiotropic. Pleiotropic enhancers are more constrained and have distinctive structural features when compared with tissue-specific enhancers. The extent of pleiotropy in enhancer function weakens the commonly held view of enhancers as being strictly tissue-specific regulatory elements. Comprehensive screens of enhancer activity and transcription factor binding site function over multiple contexts and across organisms will shed light on the mechanisms underlying enhancer pleiotropy