Transcription decouples estrogen-dependent changes in enhancer-promoter contact frequencies and spatial proximity.
PLoS Genet
; 20(5): e1011277, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38781242
ABSTRACT
How enhancers regulate their target genes in the context of 3D chromatin organization is extensively studied and models which do not require direct enhancer-promoter contact have recently emerged. Here, we use the activation of estrogen receptor-dependent enhancers in a breast cancer cell line to study enhancer-promoter communication at two loci. This allows high temporal resolution tracking of molecular events from hormone stimulation to efficient gene activation. We examine how both enhancer-promoter spatial proximity assayed by DNA fluorescence in situ hybridization, and contact frequencies resulting from chromatin in situ fragmentation and proximity ligation, change dynamically during enhancer-driven gene activation. These orthogonal methods produce seemingly paradoxical results:
upon enhancer activation enhancer-promoter contact frequencies increase while spatial proximity decreases. We explore this apparent discrepancy using different estrogen receptor ligands and transcription inhibitors. Our data demonstrate that enhancer-promoter contact frequencies are transcription independent whereas altered enhancer-promoter proximity depends on transcription. Our results emphasize that the relationship between contact frequencies and physical distance in the nucleus, especially over short genomic distances, is not always a simple one.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromatin
/
Enhancer Elements, Genetic
/
Promoter Regions, Genetic
/
Estrogens
Limits:
Female
/
Humans
Language:
En
Journal:
PLoS Genet
Journal subject:
GENETICA
Year:
2024
Type:
Article
Affiliation country:
United kingdom