RNA polymerase II dynamics shape enhancer-promoter interactions.
Nat Genet
; 55(8): 1370-1380, 2023 08.
Article
in En
| MEDLINE
| ID: mdl-37430091
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA Polymerase II
/
Enhancer Elements, Genetic
Type of study:
Prognostic_studies
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
2023
Document type:
Article
Affiliation country: