Enhancer RNAs Mediate Estrogen-Induced Decommissioning of Selective Enhancers by Recruiting ERα and Its Cofactor.
Cell Rep
; 31(12): 107803, 2020 06 23.
Article
en En
| MEDLINE
| ID: mdl-32579929
ABSTRACT
The function of enhancer RNAs (eRNAs) in transcriptional regulation remains obscure. By analyzing the genome-wide nascent transcript profiles in breast cancer cells, we identify a special group of eRNAs that are essential for estrogen-induced transcriptional repression. Using eRNAs of TM4SF1 and EFEMP1 as the paradigms, we find that these RNA molecules not only stabilize promoter-enhancer interactions but also recruit liganded estrogen receptor α (ERα) to particular enhancer regions, facilitate the formation of a functional transcriptional complex, and cause gene silencing. Interestingly, ERα is shown to directly bind with eRNAs by its DNA-binding domain. These eRNAs help with the formation of a specific ERα-centered transcriptional complex and promote the association of the histone demethylase KDM2A, which dismisses RNA polymerase II from designated enhancers and suppresses the transcription of target genes. Our work demonstrates a complete mechanism underlying the action of eRNAs in modulating and refining the locus-specific transcriptional program.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ARN
/
Elementos de Facilitación Genéticos
/
Receptor alfa de Estrógeno
/
Estrógenos
Límite:
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos