Reading the Covalent Topoisomerase1-DNA Intermediate: A Transcriptional Code Broadly Required for Signal-dependent Enhancer Activation [Human CUT&RUN]

Acutely activated enhancers require the actions of Topo1cc, including those induced by 17β-oestradiol (E2), dihydrotestosterone (DHT) and tumor necrosis factor alpha (TNFa). Topo1cc at these acutely activated enhancers is “read” by Ku70, which in this context serves as a required transcriptional coactivator, based on nucleating a Ku70/heterochromatin protein1 gamma (HP1γ) complex to facilitate the recruitment of mediator subunit Med26 for eRNA transcription. CUT&RUN experiments were designed to disclose the presence of Topo1cc at acutely activated enhancers.