How PARP1 Protects the Dnmt1 Promoter from Methylation
Author Information
Author(s): Zampieri Michele, Passananti Claudio, Calabrese Roberta, Perilli Mariagrazia, Corbi Nicoletta, De Cave Fabiana, Guastafierro Tiziana, Bacalini Maria Giulia, Reale Anna, Amicosante Gianfranco, Calabrese Lilia, Zlatanova Jordanka, Caiafa Paola
Primary Institution: Department of Cellular Biotechnologies and Hematology, Second Faculty of Medicine, University “La Sapienza”, Rome, Italy
Hypothesis
The balance between unmodified and PARylated forms of Parp1 determines the maintenance of DNA methylation patterns.
Conclusion
The study suggests that PARylated Parp1 protects the Dnmt1 promoter from methylation, and its deregulation can lead to widespread hypomethylation characteristic of cancer cells.
Supporting Evidence
- The absence of ADP-ribose polymers leads to aberrant methylation of the Dnmt1 promoter.
- Chromatin immunoprecipitation results show that Parp1 occupies the Dnmt1 promoter in normal cells.
- Over-expression of PARG results in down-regulation of Dnmt1 expression.
Takeaway
This study shows that a protein called Parp1 helps keep a part of our DNA from getting too many chemical tags that can turn genes off, and if this balance is messed up, it can lead to problems like cancer.
Methodology
The study used ectopic over-expression of PARG in L929 mouse fibroblast cells to analyze the effects on Dnmt1 expression and DNA methylation patterns.
Digital Object Identifier (DOI)
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