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TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation.

Tolić, Anja; Ravichandran, 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

(London: BioMed Central Ltd, 2022)

TY  - JOUR
AU  - Tolić, Anja
AU  - Ravichandran, Mirunalini
AU  - Rajić, Jovana
AU  - Đorđević, Marija
AU  - Đorđević, Miloš
AU  - Dinić, Svetlana
AU  - Grdović, Nevena
AU  - Arambašić Jovanović, Jelena
AU  - Mihailović, Mirjana
AU  - Nestorović, Nataša
AU  - Jurkowski, Tomasz P.
AU  - Uskoković, Aleksandra
AU  - Vidaković, Melita
PY  - 2022
UR  - https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-022-00445-8
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8985375
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4957
AB  - 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.
PB  - London: BioMed Central Ltd
T2  - Epigenetics & Chromatin
T1  - TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation.
IS  - 1
VL  - 15
DO  - 10.1186/s13072-022-00445-8
SP  - 11
ER  - 
@article{
author = "Tolić, Anja and Ravichandran, Mirunalini and Rajić, Jovana and Đorđević, Marija and Đorđević, Miloš and Dinić, Svetlana and Grdović, Nevena and Arambašić Jovanović, Jelena and Mihailović, Mirjana and Nestorović, Nataša and Jurkowski, Tomasz P. and Uskoković, Aleksandra and Vidaković, Melita",
year = "2022",
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.",
publisher = "London: BioMed Central Ltd",
journal = "Epigenetics & Chromatin",
title = "TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation.",
number = "1",
volume = "15",
doi = "10.1186/s13072-022-00445-8",
pages = "11"
}
Tolić, A., Ravichandran, M., Rajić, J., Đorđević, M., Đorđević, M., Dinić, S., Grdović, N., Arambašić Jovanović, J., Mihailović, M., Nestorović, N., Jurkowski, T. P., Uskoković, A.,& Vidaković, M.. (2022). TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation.. in Epigenetics & Chromatin
London: BioMed Central Ltd., 15(1), 11.
https://doi.org/10.1186/s13072-022-00445-8
Tolić A, Ravichandran M, Rajić J, Đorđević M, Đorđević M, Dinić S, Grdović N, Arambašić Jovanović J, Mihailović M, Nestorović N, Jurkowski TP, Uskoković A, Vidaković M. TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation.. in Epigenetics & Chromatin. 2022;15(1):11.
doi:10.1186/s13072-022-00445-8 .
Tolić, Anja, Ravichandran, 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, "TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation." in Epigenetics & Chromatin, 15, no. 1 (2022):11,
https://doi.org/10.1186/s13072-022-00445-8 . .
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