Expanding the repertoire of glucocorticoid receptor target genes by engineering genomic response elements.

ABSTRACT: The glucocorticoid receptor (GR), a hormone-activated transcription factor, binds to a myriad of genomic binding sites yet seems to regulate a much smaller number of genes. Genome-wide analysis of GR binding and gene regulation has shown that the likelihood of GR-dependent regulation increases with decreased distance of its binding to the transcriptional start site of a gene. To test if we can adopt this knowledge to expand the repertoire of GR target genes, we used CRISPR/Cas-mediated homology-directed repair to add a single GR-binding site directly upstream of the transcriptional start site of each of four genes. To our surprise, we found that the addition of a single GR-binding site can be enough to convert a gene into a GR target. The gain of GR-dependent regulation was observed for tw

SUBMITTER: Thormann V 

PROVIDER: S-EPMC6417287 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature