Ligand-Dependent Enhancer Activation Regulated by Topoisomerase-I Activity

ABSTRACT: The discovery that enhancers are regulated transcription units, encoding eRNAs, has raised new questions about the mechanisms of their activation. Here, we report an unexpected molecular mechanism that underlies ligand-dependent enhancer activation, based on DNA nicking to relieve torsional stress from eRNA synthesis. Using dihydrotestosterone (DHT)-induced binding of androgen receptor (AR) to prostate cancer cell enhancers as a model, we show rapid recruitment, within minutes, of DNA topoisomerase I (TOP1) to a large cohort of AR-regulated enhancers. Furthermore, we show that the DNA nicking activity of TOP1 is a prerequisite for robust eRNA synthesis and enhancer activation and is kinetically accompanied by the recruitment of ATR and the MRN complex, followed by additional components of

ORGANISM(S): Homo sapiens

SUBMITTER: Michael Rosenfeld 

PROVIDER: E-GEOD-63202 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress