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

Tolic, Anja, Rajic, Jovana, Djordjevic, Marija, Djordjevic, Milos, Dinic, Svetlana, Grdovic, Nevena, Arambasic-Jovanovic, Jelena, Mihailovic, Mirjana, Poznanovic, Goran, Jurkowski, Tomasz, Vidakovic, Melita and Uskokovic, Aleksandra 2019. Enrichment of Cxcl12 promoter with TET2: A possible link between promoter demethylation and enhanced gene expression in the absence of PARP-1. Archives of Biological Sciences 71 (3) , p. 455. 10.2298/ABS190404027T

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Abstract

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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
Publisher: INST BIOLOSKA ISTRAZIVANJA SIN
ISSN: 0354-4664
Date of First Compliant Deposit: 9 January 2020
Date of Acceptance: 18 April 2019
Last Modified: 13 Jan 2020 12:15
URI: http://orca.cf.ac.uk/id/eprint/128402

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