Transcription imparts architecture, function and logic to enhancer units.
Nat Genet
; 52(10): 1067-1075, 2020 10.
Article
in En
| MEDLINE
| ID: mdl-32958950
ABSTRACT
Distal enhancers play pivotal roles in development and disease yet remain one of the least understood regulatory elements. We used massively parallel reporter assays to perform functional comparisons of two leading enhancer models and find that gene-distal transcription start sites are robust predictors of active enhancers with higher resolution than histone modifications. We show that active enhancer units are precisely delineated by active transcription start sites, validate that these boundaries are sufficient for capturing enhancer function, and confirm that core promoter sequences are necessary for this activity. We assay adjacent enhancers and find that their joint activity is often driven by the stronger unit within the cluster. Finally, we validate these results through functional dissection of a distal enhancer cluster using CRISPR-Cas9 deletions. In summary, definition of high-resolution enhancer boundaries enables deconvolution of complex regulatory loci into modular units.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
/
Enhancer Elements, Genetic
/
Transcription Initiation Site
/
Histone Code
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
2020
Document type:
Article
Affiliation country:
Estados Unidos