Enrichment of Cxcl12 promoter with TET2: A possible link between promoter demethylation and enhanced gene expression in the absence of PARP-1

Autor: Jelena Arambasic-Jovanovic, Anja Tolić, Milos Djordjevic, Tomasz P. Jurkowski, Mirjana Mihailović, Melita Vidaković, Svetlana Dinić, Goran Poznanović, Jovana Rajić, Marija Prekajski Djordjevic, Aleksandra Uskoković, Nevena Grdović
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Archives of Biological Sciences, Vol 71, Iss 3, Pp 455-462 (2019)
Archives of Biological Sciences
ISSN: 1821-4339
0354-4664
Popis: 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. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 173020]
Databáze: OpenAIRE