Transcription elongation regulates genome 3D structure

How transcription affects genome organization in the nucleus is poorly understood. Analyzing influenza A virus (IAV)-infected human macrophages, we observe rapid reorganization of chromatin interactions. These changes occur where IAV NS1 protein-induced global inhibition of transcription termination leads to read-through transcription for hundreds of kilobases past the ends of highly transcribed genes. In these read-through regions, RNA polymerase II induces cohesin displacement from CTCF sites at loop anchors, leading to disrupted chromatin interactions and decompaction. Conversely, transcription elongation inhibition allows cohesin to accumulate at previously transcribed CTCF sites and to mediate chromatin looping and compaction. Data from non-viral stimuli indicates that transcription generally regulates cohesin and genome organization within gene bodies. Additionally, transcription into heterochromatin regions switches them from the inert (B) to the permissive (A) chromatin compartment and enables transcription factor binding. Our data indicate that transcription elongation by RNA polymerase II remodels genome architecture in vivo.