Human genome-wide measurement of drug-responsive regulatory activity.

ABSTRACT: Environmental stimuli commonly act via changes in gene regulation. Human-genome-scale assays to measure such responses are indirect or require knowledge of the transcription factors (TFs) involved. Here, we present the use of human genome-wide high-throughput reporter assays to measure environmentally-responsive regulatory element activity. We focus on responses to glucocorticoids (GCs), an important class of pharmaceuticals and a paradigmatic genomic response model. We assay GC-responsive regulatory activity across >10⁸ unique DNA fragments, covering the human genome at >50×. Those assays directly detected thousands of GC-responsive regulatory elements genome-wide. We then validate those findings with measurements of transcription factor occupancy, histone modifications, chroma

SUBMITTER: Johnson GD 

PROVIDER: S-EPMC6303339 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature