RNA polymerase II and PARP1 shape enhancer-promoter contacts

Barshad, G.; Lewis, J. J.; Chivu, A. G.; Abuhashem, A.; Krietenstein, N.; Rice, E. J.; Rando, O. J.; Hadjantonakis, A.-K.; Danko, C. G.

doi:10.1101/2022.07.07.499190

bioRxiv · 10.1101/2022.07.07.499190

RNA polymerase II and PARP1 shape enhancer-promoter contacts

Barshad, G.·Lewis, J. J.·Chivu, A. G.·Abuhashem, A.·Krietenstein, N.·Rice, E. J.·Rando, O. J.·Hadjantonakis, A.-K.·Danko, C. G.

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Abstract

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.

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Barshad, G., Lewis, J. J., Chivu, A. G., Abuhashem, A., Krietenstein, N., Rice, E. J., Rando, O. J., Hadjantonakis, A.-K., Danko, C. G.. 2022-07-08. RNA polymerase II and PARP1 shape enhancer-promoter contacts. https://doi.org/10.1101/2022.07.07.499190

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