Losing DNA methylation at repetitive elements and breaking bad

Abstract

Background DNA methylation is an epigenetic chromatin mark that allows heterochromatin formation and gene silencing. It has a fundamental role in preserving genome stability (including chromosome stability) by controlling both gene expression and chromatin structure. Therefore, the onset of an incorrect pattern of DNA methylation is potentially dangerous for the cells. This is particularly important with respect to repetitive elements, which constitute the third of the human genome. Main body Repetitive sequences are involved in several cell processes, however, due to their intrinsic nature, they can be a source of genome instability. Thus, most repetitive elements are usually methylated to maintain a heterochromatic, repressed state. Notably, there is increasing evidence showing that repetitive elements (satellites, long interspersed nuclear elements (LINEs), Alus) are frequently hypomethylated in various of human pathologies, from cancer to psychiatric disorders. Repetitive sequences’ hypomethylation correlates with chromatin relaxation and unscheduled transcription. If these alterations are directly involved in human diseases aetiology and how, is still under investigation. Conclusions Hypomethylation of different families of repetitive sequences is recurrent in many different human diseases, suggesting that the methylation status of these elements can be involved in preservation of human health. This provides a promising point of view towards the research of therapeutic strategies focused on specifically tuning DNA methylation of DNA repeats.

Organization of the Cytoskeleton in Ectopic Foci of the Endometrium with Rare Localization

“…In general, an increase in genome methylation is associated more often with a decrease in the expression level as a result of tighter binding of methylated DNA to the nucleosome [51,52]. Nevertheless, some genes can avoid this and be hypomethylated during general hypermethylation, both in various diseases and during adaptation to extreme conditions [53][54][55], demonstrating a high level of expression against the background of transcriptional silencing, which may explain the high level of expression of ACTN1 in the described cases of endometriosis. For example, for alpha-actinin1 in the tissues of the heart, lungs, and testes under conditions of weightlessness simulation, it was shown that CpG islands in the promoter region avoid global methylation and the expression of ACTN1 in these cases increases [54].…”

Transcriptome Architecture of Osteoblastic Cells Infected With Staphylococcus aureus Reveals Strong Inflammatory Responses and Signatures of Metabolic and Epigenetic Dysregulation

“…All of these changes could result in hypomethylation of certain loci and lasting imprints of infection. Hypomethylation may also induce genomic instability ( Pappalardo and Barra, 2021 ). We also observed down-regulation of several HDACs ( HDAC4 , 6, and 10) suggesting decreased histone deacetylation, which is essential for histone-DNA interaction.…”

Comprehensive DNA Methylation Analysis of Human Neuroblastoma Cells Treated With Haloperidol and Risperidone

“…This was also concordant with a previous study that revealed an association of haloperidol and increased global DNA methylation levels in leukocytes ( Melas et al, 2012 ). It should be noted that the possible role of intergenic DNA methylation is to repress the activity of harmful genetic elements such as transposons ( Pappalardo and Barra, 2021 ). DNA methylation of the gene body is also associated with altered gene expressions ( Moore et al, 2013 ).…”