PT - JOURNAL ARTICLE AU - Gilad Barshad AU - James J. Lewis AU - Alexandra G. Chivu AU - Abderhman Abuhashem AU - Nils Krietenstein AU - Edward J. Rice AU - Oliver J. Rando AU - Anna-Katerina Hadjantonakis AU - Charles G. Danko TI - RNA polymerase II and PARP1 shape enhancer-promoter contacts AID - 10.1101/2022.07.07.499190 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.07.07.499190 4099 - http://biorxiv.org/content/early/2022/07/08/2022.07.07.499190.short 4100 - http://biorxiv.org/content/early/2022/07/08/2022.07.07.499190.full AB - How enhancers control target gene expression over long genomic distances remains an important unsolved problem. Here we studied enhancer-promoter contact architecture and communication by integrating data from nucleosome-resolution genomic contact maps, nascent transcription, and perturbations to transcription-associated proteins and thousands of candidate enhancers. Contact frequency between functionally validated enhancer-promoter pairs was most enriched near the +1 and +2 nucleosomes at enhancers and target promoters, indicating that functional enhancer-promoter pairs spend time in close physical proximity. Blocking RNA polymerase II (Pol II) caused major disruptions to enhancer-promoter contacts. Paused Pol II occupancy and the enzymatic activity of poly (ADP-ribose) polymerase 1 (PARP1) stabilized enhancer-promoter contacts. Based on our findings, we propose an updated model that couples transcriptional dynamics and enhancer-promoter communication.Competing Interest StatementThe authors have declared no competing interest.