Comparative analysis of epigenetic inhibitors reveals different degrees of interference with transcriptional gene silencing and induction of DNA damage
Anna Nowicka , Barbara Tokarz , Jana Zwyrtková , Eva Dvořák Tomaštíková , Klára Procházková , Ugur Ercan , Andreas Finke , Wilfried Rozhon , Brigitte Poppenberger , Miroslav Otmar , Igor Niezgodzki , Marcela Krečmerová , Ingo Schubert , Ales Pecinka
AbstractRepetitive DNA sequences and some genes are epigenetically repressed by transcriptional gene silencing (TGS). When genetic mutants are not available or problematic to use, TGS can be suppressed by chemical inhibitors. However, informed use of epigenetic inhibitors is partially hampered by the absence of any systematic comparison. In addition, there is emerging evidence that epigenetic inhibitors cause genomic instability, but the nature of this damage and its repair remain unclear. To bridge these gaps, we compared the effects of 5-azacytidine (AC), 20-deoxy-5-azacytidine (DAC), zebularine and 3-deazaneplanocin A (DZNep) on TGS and DNA damage repair. The most effective inhibitor of TGS was DAC, followed by DZNep, zebularine and AC. We conﬁrmed that all inhibitors induce DNA damage and suggest that this damage is repaired by multiple pathways with a critical role of homologous recombination and of the SMC5/6 complex. A strong positive link between the degree of cytidine analog-induced DNA demethylation and the amount of DNA damage suggests that DNA damage is an integral part of cytidine analog-induced DNA demethylation. This helps us to understand the function of DNA methylation in plants and opens the possibility of using epigenetic inhibitors in biotechnology.
|Journal series||Plant Journal, ISSN 0960-7412, e-ISSN 1365-313X, (N/A 140 pkt)|
|Publication size in sheets||0.3|
|Keywords in English||DNA methylation, genome stability, DNA damage, cytidine analog, epigenetic inhibitors, Arabidopsis thaliana, Vicia faba|
|ASJC Classification||; ;|
|Publication indicators||: 2017 = 1.669; : 2018 = 5.726 (2) - 2018=6.467 (5)|
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