Zebrafish as a model to determine conserved gene regulatory mechanisms in vertebrates

Super-enhancers and CTCF are considered as central players in the organization of mammalian genomes that directly impact the regulation of gene expression. Here, to gain insight into their functional conservation, analyses of super-enhancers and CTCF in zebrafish were performed. Super-enhancers annotated in zebrafish show high cell and tissue specificity, and the main difference identified when compared to mammalian super-enhancers is their distribution relative to transcription start sites. Conservation analyses indicate that super-enhancers do not have higher sequence conservation than typical enhancers. By restricting the analysis to those super-enhancers associated with orthologs, a subset of super-enhancers that have higher sequence conservation than the rest was identified. Comparison of the expression patterns driven by constitutive regions of two of these super-enhancers enabled the identification of regions controlling similar expression patterns in spite of no evident sequence conservation. Analyses of CTCF peaks that overlap promoters indicate a correlation between the abundance of CTCF and gene expression, which could be explained by blockage of nucleosome deposition at those promoters. In summary, these results show evidence of conserved and divergent functions of gene regulators in vertebrates and set a precedent for studies of genome organization in zebrafish.