DNA Methylation in Huntington’s Disease

Abstract

Methylation of cytosine in CpG dinucleotides is the major DNA modification in mammalian cells that is a key component of stable epigenetic marks. This modification, which on the one hand is reversible, while on the other hand, can be maintained through successive rounds of replication plays roles in gene regulation, genome maintenance, transgenerational epigenetic inheritance, and imprinting. Disturbed DNA methylation contributes to a wide array of human diseases from single-gene disorders to sporadic metabolic diseases or cancer. DNA methylation was also shown to affect several neurodegenerative disorders, including Huntington’s disease (HD), a fatal, monogenic inherited disease. HD is caused by a polyglutamine repeat expansion in the Huntingtin protein that brings about a multifaceted pathogenesis affecting several cellular processes. Research of the last decade found complex, genome-wide DNA methylation changes in HD pathogenesis that modulate transcriptional activity and genome stability. This article reviews current evidence that sheds light on the role of DNA methylation in HD.

Therapeutic effects of resveratrol on epigenetic mechanisms in age‐related diseases: A comprehensive review

“…Research surrounding neurodegenerative ailments such as Alzheimer's Disease has demonstrated generalized hypermethylation of brain tissues, coupled with an elevated presence of 5‐hydroxymethylcytosine (5hmC) in the afflicted cells (Coppieters et al, 2014). Despite that, in Parkinson's and Huntington's diseases both hyper and hypo‐methylation of DNA can be observed (it depends on the gene promotor site) (Wüllner et al, 2016; Zsindely et al, 2021). Cancer is also another example of an age‐related disease that is affected by altered DNA methylation patterns.…”

Epigenetic modification: A novel insight into diabetic wound healing

“…During the 5 mC to cytosine conversion, intermediate products are generated, such as 5caC, 5 fC, and 5hmC. However, recent studies have found that certain products exist stably and modulate diseases [ 115 ]. However, due to the paucity of literature on intermediates, the focus of this study will be on 5 mC in diabetic wound repair.…”

Distinctive Patterns of 5-Methylcytosine and 5-Hydroxymethylcytosine in Schizophrenia

“…Abnormalities of 5mC have been widely reported in neurodegenerative diseases, such as Parkinson’s disease (PD) and Huntington’s disease (HD) [ 18 , 19 , 20 ]. Psychiatric disorders are characterized by impairment in cognition, emotion regulation, or behavior, and typically include bipolar disorder (BD) and schizophrenia.…”