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

Oxidative Medicine and Cellular Longevity
Michalina WezykCezary Żekanowski

Abstract

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 af...Continue Reading

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Jul 23, 2019·Critical Reviews in Clinical Laboratory Sciences·Peter D Fransquet, Joanne Ryan
Nov 7, 2019·Stem Cells and Development·Valentina V Nenasheva, Vyacheslav Z Tarantul
May 27, 2020·Journal of Forensic Sciences·Alberto MontesantoGiuseppe Passarino
Aug 4, 2020·Neuroscience Insights·Tessa Bergsma, Ekaterina Rogaeva
Sep 25, 2020·International Journal of Molecular Sciences·Banaja P DashAndreas Hermann
Mar 21, 2020·International Journal of Molecular Sciences·Jose A SantiagoJudith A Potashkin
Jan 12, 2020·BioFactors·Xiaoyan ChenHeng Zhang
Oct 10, 2021·Human Cell·Guoxing XuJiangbo Zhong

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Methods Mentioned

BETA
biopsies
RNA-seq
Assay
Ubiquitination

Software Mentioned

Reactome
Subread tool
IPA
R Bioconductor
Ingenuity Pathway Analysis ( IPA )
Search Tool for the Retrieval of Interacting ( STRING
STAR mapper
Cuffdiff
STRING
edgeR

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