TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation.
2022
Autori:
Tolić, AnjaRavichandran, Mirunalini
Rajić, Jovana
Đorđević, Marija
Đorđević, Miloš
Dinić, Svetlana
Grdović, Nevena
Arambašić Jovanović, Jelena
Mihailović, Mirjana
Nestorović, Nataša
Jurkowski, Tomasz P.
Uskoković, Aleksandra
Vidaković, Melita
Tip dokumenta:
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
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.
Ključne reči:
5-Hydroxymethylcytosine; DNA demethylation; PARP; PARylation; TETIzvor:
Epigenetics & Chromatin, 2022, 15, 1, 11-Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200007 (Univerzitet u Beogradu, Institut za biološka istraživanja 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- COST Actions TD0509
- COST Actions CM1406
- COST Actions CA16119
DOI: 10.1186/s13072-022-00445-8
ISSN: 1756-8935
PubMed: 35382873
WoS: 000779007000001
Scopus: 2-s2.0-85127538420
URI
https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-022-00445-8http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8985375
http://radar.ibiss.bg.ac.rs/handle/123456789/4957