Characterization of a functional endothelial super-enhancer that regulates ADAMTS18 and angiogenesis.

ABSTRACT: Super-enhancers are clusters of enhancers associated with cell lineage. They can be powerful gene-regulators and may be useful in cell-type specific viral-vector development. Here, we have screened for endothelial super-enhancers and identified an enhancer from within a cluster that conferred 5-70-fold increase in transgene expression. Importantly, CRISPR/Cas9 deletion of enhancers demonstrated regulation of ADAMTS18, corresponding to evidence of chromatin contacts between these genomic regions. Cell division-related pathways were primarily affected by the enhancer deletions, which correlated with significant reduction in cell proliferation. Furthermore, we observed changes in angiogenesis-related genes consistent with the endothelial specificity of this SE. Indeed, deletion of the enhance

SUBMITTER: Mushimiyimana I 

PROVIDER: S-EPMC8373076 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature