RT Journal Article
SR Electronic
T1 RNA polymerase II and PARP1 shape enhancer-promoter contacts
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.07.07.499190
DO 10.1101/2022.07.07.499190
A1 Gilad Barshad
A1 James J. Lewis
A1 Alexandra G. Chivu
A1 Abderhman Abuhashem
A1 Nils Krietenstein
A1 Edward J. Rice
A1 Oliver J. Rando
A1 Anna-Katerina Hadjantonakis
A1 Charles G. Danko
YR 2022
UL http://biorxiv.org/content/early/2022/07/08/2022.07.07.499190.abstract
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.