RNA polymerase II dynamics shape enhancer-promoter interactions.
| Publication Type | Academic Article |
| Authors | Barshad G, Lewis J, Chivu A, Abuhashem A, Krietenstein N, Rice E, Ma Y, Wang Z, Rando O, Hadjantonakis A, Danko C |
| Journal | Nat Genet |
| Volume | 55 |
| Issue | 8 |
| Pagination | 1370-1380 |
| Date Published | 07/10/2023 |
| ISSN | 1546-1718 |
| Keywords | RNA Polymerase II, Enhancer Elements, Genetic |
| Abstract | How enhancers control target gene expression over long genomic distances remains an important unsolved problem. Here we investigated enhancer-promoter communication by integrating data from nucleosome-resolution genomic contact maps, nascent transcription and perturbations affecting either RNA polymerase II (Pol II) dynamics or the activity of thousands of candidate enhancers. Integration of new Micro-C experiments with published CRISPRi data demonstrated that enhancers spend more time in close proximity to their target promoters in functional enhancer-promoter pairs compared to nonfunctional pairs, which can be attributed in part to factors unrelated to genomic position. Manipulation of the transcription cycle demonstrated a key role for Pol II in enhancer-promoter interactions. Notably, promoter-proximal paused Pol II itself partially stabilized interactions. We propose an updated model in which elements of transcriptional dynamics shape the duration or frequency of interactions to facilitate enhancer-promoter communication. |
| DOI | 10.1038/s41588-023-01442-7 |
| PubMed ID | 37430091 |
| PubMed Central ID | PMC10714922 |