title: The Functionality and Evolution of Eukaryotic Transcriptional Enhancers.
abstract: Enhancers regulate precise spatial and temporal patterns of gene expression in eukaryotes and, moreover, evolutionary changes in these modular cis-regulatory elements may represent the predominant genetic basis for phenotypic evolution. Here, we review approaches to identify and functionally analyze enhancers and their transcription factor binding sites, including assay for transposable-accessible chromatin-sequencing (ATAC-Seq) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9, respectively. We also explore enhancer functionality, including how transcription factor binding sites combine to regulate transcription, as well as research on shadow and super enhancers, and how enhancers can act over great distances and even in trans. Finally, we discuss recent theoretical and empirical data on how transcription factor binding sites and enhancers evolve. This includes how the function of enhancers is maintained despite the turnover of transcription factor binding sites as well as reviewing studies where mutations in enhancers have been shown to underlie morphological change.
authors.affiliation: Oxford Brookes University, Oxford, United Kingdom.
authors.forename: A D
authors.initials: AD
authors.lastname: Buffry
authors.affiliation: Oxford Brookes University, Oxford, United Kingdom.
authors.forename: C C
authors.initials: CC
authors.lastname: Mendes
authors.affiliation: Oxford Brookes University, Oxford, United Kingdom.
authors.forename: A P
authors.initials: AP
authors.lastname: McGregor
mesh_terms: D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D004330:Drosophila / Q000235:genetics; D004742:Enhancer Elements, Genetic; D056890:Eukaryota / Q000235:genetics*; D019143:Evolution, Molecular; D015870:Gene Expression; D006801:Humans; D051379:Mice; D038621:Regulatory Sequences, Ribonucleic Acid; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D038621:Regulatory Sequences, Ribonucleic Acid; D014157:Transcription Factors
keywords: Binding sites; Evolution; Gene expression; Modularity; Transcription factors; cis-Regulatory sequences