Enrichment of Cxcl12 promoter with TET2: a possible link between promoter demethylation and enhanced gene expression in the absence of PARP-1
2019
Autori:
Tolić, AnjaRajić, Jovana
Đorđević, Marija
Đorđević, Miloš
Dinić, Svetlana
Grdović, Nevena
Arambašić Jovanović, Jelena
Mihailović, Mirjana
Poznanović, Goran
Jurkowski, Tomasz P.
Vidaković, Melita
Uskoković, Aleksandra
Tip dokumenta:
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
Previously, we described the link between C-X-C motif chemokine 12 (Cxcl12) gene induction
and DNA hypomethylation in the absence of poly(ADP-ribose) polymerase 1 (PARP-1). We have now
firmly established that demethylation is the primary cause of gene induction on the basis of Cxcl12 gene
upregulation upon treatment with the demethylating agent 5-azacytidine (5-aza). Since the demethylation
state of Cxcl12 is favored by PARP-1 absence, we investigated the presence of ten-eleven translocation
(TET) proteins on the Cxcl12 promoter in order to corroborate the relationship between the demethylation
process and increased gene expression that occurs in the absence of PARP-1. Analysis was performed on the promoter region within CpG islands of Cxcl12 from control mouse embryonic fibroblasts (NIH3T3)
and PARP-1 knock-out mouse embryonic fibroblasts (PARP1-/-). The lack of PARP-1 increased the abundance of TET2 on the Cxcl12 promoter, suggesting that TET-mediated demethylation provoked by the absence of PARP-1 could account for the observed increased expression of this chemokine. Deciphering the regulation of DNA (de)methylation factors that control Cxcl12 expression may provide an additional therapeutic approach in pharmacological interventions where gene switching on or off based on targeted stimulation or inhibition is necessary.
Ključne reči:
DNA demethylation; 5-aza; TET2; PARP-1; CXCL12Izvor:
Archives of Biological Sciences, 2019, 71, 3, 455-462Finansiranje / projekti:
- Signalni molekuli u dijabetesu: identifikacija potencijalnih bioloških markera uključenih u modifikaciju i integraciju signalnih puteva u cilju predikcije i intervencije u dijabetesu (RS-MESTD-Basic Research (BR or ON)-173020)
- Alexander von Humboldt foundation, program for funding a Research Group Linkage (to MV and TJ - 2015/2016)
DOI: 10.2298/ABS190404027T
ISSN: 03544664