How studying enhancer evolution may provide insight into enhancer grammar.

Abstract

Changes in the coding sequences of genes do not fully explain the phenotypic differences observed between and within species. It is known that changes in enhancers, the non-coding cis-regulatory regions controlling these genes, also contribute to these differences. However, the mechanisms by which enhancers regulate gene expression are still poorly understood. Enhancer grammar is the set of rules governing how the sequence and organization of enhancers affect spatio-temporal gene expression. In this literature review I discuss several models of enhancer grammar, approaches to studying enhancer grammar, and postulate how studying enhancer evolution could provide clues for eventually solving enhancer grammar. Although the application of this approach appears to be limited to evolutionarily conserved enhancers, the data generated by studying the evolution of less-conserved enhancers may be of great use for developing machine learning strategies aiming to identify enhancer function.