Journal of cellular and molecular medicine, 2019-04, Vol.23 (4), p.2610-2618
2019
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- Autor(en) / Beteiligte
- Titel
- Absence of PARP‐1 affects Cxcl12 expression by increasing DNA demethylation
- Ist Teil von
- Journal of cellular and molecular medicine, 2019-04, Vol.23 (4), p.2610-2618
- Ort / Verlag
- England: John Wiley & Sons, Inc
- Erscheinungsjahr
- 2019
- Quelle
- Access via Wiley Online Library
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1582-1838eISSN: 1582-4934DOI: 10.1111/jcmm.14154Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6433732
- Format
- –
- Schlagworte
- 5' Untranslated Regions, Adenosine diphosphate, Animals, Cell culture, Chemokine CXCL12 - genetics, Chemokine CXCL12 - metabolism, Chemokines, CpG Islands, CXCL12, CXCL12 protein, Demethylation, Deoxyribonucleic acid, DNA, DNA - genetics, DNA - metabolism, DNA demethylation, DNA Methylation, DNA repair, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Embryo fibroblasts, Embryos, Enzymes, Epigenesis, Genetic, Epigenetics, Exons, Fibroblasts, Gene expression, Introns, Mice, Mice, Knockout, Molecular weight, NIH 3T3 Cells, Original, PARP‐1, Poly (ADP-Ribose) Polymerase-1 - deficiency, Poly (ADP-Ribose) Polymerase-1 - genetics, Poly(ADP-ribose) polymerase, Promoter Regions, Genetic, Proto-Oncogene Proteins - genetics, Proto-Oncogene Proteins - metabolism, Ribose, Signal Transduction, Software, TETs, Transcription, Translocation