TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation.
Epigenetics Chromatin
; 15(1): 11, 2022 04 05.
Article
en En
| MEDLINE
| ID: mdl-35382873
ABSTRACT
BACKGROUND:
Poly(ADP-ribosyl)ation (PARylation), a posttranslational modification introduced by PARP-1 and PARP-2, has first been implicated in DNA demethylation due to its role in base excision repair. Recent evidence indicates a direct influence of PARP-dependent PARylation on TET enzymes which catalyse hydroxymethylation of DNA-the first step in DNA demethylation. However, the exact nature of influence that PARylation exerts on TET activity is still ambiguous. In our recent study, we have observed a negative influence of PARP-1 on local TET-mediated DNA demethylation of a single gene and in this study, we further explore PARP-TET interplay.RESULTS:
Expanding on our previous work, we show that both TET1 and TET2 can be in vitro PARylated by PARP-1 and PARP-2 enzymes and that TET1 PARylation negatively affects the TET1 catalytic activity in vitro. Furthermore, we show that PARylation inhibits TET-mediated DNA demethylation at the global genome level in cellulo.CONCLUSIONS:
According to our findings, PARP inhibition can positively influence TET activity and therefore affect global levels of DNA methylation and hydroxymethylation. This gives a strong rationale for future examination of PARP inhibitors' potential use in the therapy of cancers characterised by loss of 5-hydroxymethylcytosine.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Inhibidores de Poli(ADP-Ribosa) Polimerasas
/
Poli ADP Ribosilación
Idioma:
En
Revista:
Epigenetics Chromatin
Año:
2022
Tipo del documento:
Article