PARP1 interacts with WDR5 to enhance target gene recognition and facilitate tumorigenesis.
Cancer Lett
; 593: 216952, 2024 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-38750719
ABSTRACT
Poly (ADP-ribose) polymerase-1 (PARP1) is a nuclear protein that attaches negatively charged poly (ADP-ribose) (PAR) to itself and other target proteins. While its function in DNA damage repair is well established, its role in target chromatin recognition and regulation of gene expression remains to be better understood. This study showed that PARP1 interacts with SET1/MLL complexes by binding directly to WDR5. Notably, although PARP1 does not modulate WDR5 PARylation or the global level of H3K4 methylation, it exerts locus-specific effects on WDR5 binding and H3K4 methylation. Interestingly, PARP1 and WDR5 show extensive co-localization on chromatin, with WDR5 facilitating the recognition and expression of target genes regulated by PARP1. Furthermore, we demonstrated that inhibition of the WDR5 Win site impedes the interaction between PARP1 and WDR5, thereby inhibiting PARP1 from binding to target genes. Finally, the combined inhibition of the WDR5 Win site and PARP shows a profound inhibitory effect on the proliferation of cancer cells. These findings illuminate intricate mechanisms underlying chromatin recognition, gene transcription, and tumorigenesis, shedding light on previously unrecognized roles of PARP1 and WDR5 in these processes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Unión Proteica
/
Regulación Neoplásica de la Expresión Génica
/
N-Metiltransferasa de Histona-Lisina
/
Péptidos y Proteínas de Señalización Intracelular
/
Poli(ADP-Ribosa) Polimerasa-1
Límite:
Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Irlanda