![](/images/graphics-bg.png)
Hypermethylation of TRIM59 and KLF14 Influences Cell Death Signaling in Familial Alzheimer’s Disease
Joint Authors
Pośpiech, Ewelina
Barcikowska-Kotowicz, Maria
Żekanowski, Cezary
Wężyk, Michalina
Spólnicka, Magdalena
Pepłońska, Beata
Zbieć-Piekarska, Renata
Ilkowski, Jan
Styczyńska, Maria
Barczak, Anna
Zboch, Marzena
Filipek-Gliszczynska, Anna
Skrzypczak, Magdalena
Ginalski, Krzysztof
Kabza, Michał
Branicki, Wojciech
Makałowska, Izabela
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-04-04
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Wężyk, Michalina& Spólnicka, Magdalena& Pośpiech, Ewelina& Pepłońska, Beata& Zbieć-Piekarska, Renata& Ilkowski, Jan…[et al.]. 2018. Hypermethylation of TRIM59 and KLF14 Influences Cell Death Signaling in Familial Alzheimer’s Disease. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-11.
https://search.emarefa.net/detail/BIM-1211879
Modern Language Association (MLA)
Wężyk, Michalina…[et al.]. Hypermethylation of TRIM59 and KLF14 Influences Cell Death Signaling in Familial Alzheimer’s Disease. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-11.
https://search.emarefa.net/detail/BIM-1211879
American Medical Association (AMA)
Wężyk, Michalina& Spólnicka, Magdalena& Pośpiech, Ewelina& Pepłońska, Beata& Zbieć-Piekarska, Renata& Ilkowski, Jan…[et al.]. Hypermethylation of TRIM59 and KLF14 Influences Cell Death Signaling in Familial Alzheimer’s Disease. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-11.
https://search.emarefa.net/detail/BIM-1211879
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1211879