Absence of PARP-1 affects Cxcl12 expression by increasing DNA demethylation
2019
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Authors:
Tolić, AnjaGrdović, Nevena
Dinić, Svetlana
Rajić, Jovana
Đorđević, Miloš
Đorđević, Marija
Arambašić Jovanović, Jelena
Mihailović, Mirjana
Poznanović, Goran
Uskoković, Aleksandra
Vidaković, Melita
Document Type:
Article (Published version)
,
© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine
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Show full item recordAbstract:
Poly [ADP-ribose] polymerase 1 (PARP-1) has an inhibitory effect on C-X-C motif chemokine 12 gene (Cxcl12) transcription. We examined whether PARP-1 affects the epigenetic control of Cxcl12 expression by changing its DNA methylation pattern. We observed increased expression of Cxcl12 in PARP-1 knock-out mouse embryonic fibroblasts (PARP1-/-) in comparison to wild-type mouse embryonic fibroblasts (NIH3T3). In the Cxcl12 gene, a CpG island is present in the promoter, the 5' untranslated region (5' UTR), the first exon and in the first intron. The methylation state of Cxcl12 in each cell line was investigated by methylation-specific PCR (MSP) and high resolution melting analysis (HRM). Both methods revealed strong demethylation in PARP1-/- compared to NIH3T3 cells in all four DNA regions. Increased expression of the Ten-eleven translocation (Tet) genes in PARP1-/- cells indicated that TETs could be important factors in Cxcl12 demethylation in the absence of PARP-1, accounting for its increased expression. Our results showed that PARP-1 was a potential upstream player in (de)methylation events that modulated Cxcl12 expression.
Keywords:
CXCL12; DNA demethylation; PARP-1; TETsSource:
Journal of Cellular and Molecular Medicine, 2019, 23, 4, 2610-2618Funding / projects:
- Signaling molecules in diabetes: search for potential targets in intrinsic pathways for prediction and intervention in diabetes (RS-MESTD-Basic Research (BR or ON)-173020)
DOI: 10.1111/jcmm.14154
ISSN: 1582-1838
PubMed: 30697918