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Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 6918797, 11 pages
Research Article

Hypermethylation of TRIM59 and KLF14 Influences Cell Death Signaling in Familial Alzheimer’s Disease

1Laboratory of Neurogenetics, Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre of the Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland
2Central Forensic Laboratory of the Police, 7 Aleje Ujazdowskie Street, 00-583 Warsaw, Poland
3Department of Genetics and Evolution, Institute of Zoology of the Jagiellonian University, 9 Gronostajowa Street, 30-387 Krakow, Poland
4Malopolska Centre of Biotechnology of the Jagiellonian University, 7A Gronostajowa Street, 30-387 Krakow, Poland
5Faculty of Health Sciences, Department of Emergency Medicine, Poznan University of Medical Sciences, 10 Fredry Street, 61-701 Poznan, Poland
6Center of Alzheimer’s Disease of Wroclaw Medical University, 12 Jana Pawla II Street, 59-330 Scinawa, Poland
7Clinical Department of Neurology, Extrapyramidal Disorders and Alzheimer’s Outpatient Clinic, Central Clinical Hospital of the Ministry of Interior in Warsaw, 137 Woloska Street, 02-507 Warsaw, Poland
8Laboratory of Bioinformatics and Systems Biology, Centre of New Technologies, University of Warsaw, 93 Zwirki i Wigury Street, 02-089 Warsaw, Poland
9Laboratory of Bioinformatics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, 89 Umultowska Street, 61-614 Poznan, Poland

Correspondence should be addressed to Michalina Wezyk; moc.liamg@ajiram.anilahcim

Received 6 October 2017; Revised 14 January 2018; Accepted 4 February 2018; Published 4 April 2018

Academic Editor: Juliana da Silva

Copyright © 2018 Michalina Wezyk et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Epigenetic mechanisms play an important role in the development and progression of various neurodegenerative diseases. Abnormal methylation of numerous genes responsible for regulation of transcription, DNA replication, and apoptosis has been linked to Alzheimer’s disease (AD) pathology. We have recently performed whole transcriptome profiling of familial early-onset Alzheimer’s disease (fEOAD) patient-derived fibroblasts. On this basis, we demonstrated a strong dysregulation of cell cycle checkpoints and DNA damage response (DDR) in both fibroblasts and reprogrammed neurons. Here, we show that the aging-correlated hypermethylation of KLF14 and TRIM59 genes associates with abnormalities in DNA repair and cell cycle control in fEOAD. Based on the resulting transcriptome networks, we found that the hypermethylation of KLF14 might be associated with epigenetic regulation of the chromatin organization and mRNA processing followed by hypermethylation of TRIM59 likely associated with the G2/M cell cycle phase and p53 role in DNA repair with BRCA1 protein as the key player. We propose that the hypermethylation of KLF14 could constitute a superior epigenetic mechanism for TRIM59 hypermethylation. The methylation status of both genes affects genome stability and might contribute to proapoptotic signaling in AD. Since this study combines data obtained from various tissues from AD patients, it reinforces the view that the genetic methylation status in the blood may be a valuable predictor of molecular processes occurring in affected tissues. Further research is necessary to define a detailed role of TRIM59 and KLF4 in neurodegeneration of neurons.