Genome-wide functional assessment of enhancer activities in the human genome

We illustrate that modifications to the previously published STARR-seq protocols are capable of assessing enhancer activity of whole genomes on mammalian systems using the human prostate cancer cell line, LNCaP. Besides detecting accessible enhancers located in open chromatin regions, we are also able to discover active, inaccessible enhancers in closed chromatin regions. By applying histone deacetylase inhibitor, trichostatin A, genes nearby the previously inaccessible enhancers are up-regulated, indicating the potential for endogenous functionality of these regulatory elements. These results exemplify how whole genome STARR-seq provides an improved approach to gain a better understanding of the intricacies of transcriptional regulation of high complexity mammalian genomes. Overall design: Profile enhancer activity of whole human genome in LNCap cells, and investigate the endogenous regulatory potential of active, inaccessible enhancers by examining gene expression and chromatin accessibility before and after trichostatin A treatment.