The Role of DNA Methylation in Human Disease – Technology Networks

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DNA methylation is one of the earliest epigenetic modifications to be discovered in human beings. It involves the transfer of methyl (CH3) groups to the C5 position of cytosine bases that comprise deoxyribonucleic acid (DNA) to produce 5-methylcytosine (5mC) – the reaction is catalyzed by a family of enzymes called DNA methyltransferases (DNMTs). Typically, the altered cytosine bases reside immediately adjacent to guanine bases. This leads to two 5mC bases sitting diagonally to each other on complementary DNA strands.

DNMTs have several distinct roles, for instance, they may function as de novo DNMTs, which involves establishing the initial pattern of methyl groups on a DNA molecule. While other DNMTs adopt maintenance roles, copying the methylation pattern from an existing DNA strand to its new partner after replication has occurred.

Several studies in the 1980s revealed that DNA methylation played a major part in both gene regulation and cell differentiation. Since then, further research has confirmed the role of abnormal methylation in the development and progression of various diseases. According to Manel Esteller, director of the Josep Carreras Leukaemia Research Institute and professor of genetics at the University of Barcelona, “DNA methylation is one of the main controllers for specific-tissue expression allowing the correct expression of a gene in the right organ or cell type.” He further added, “DNA methylation acts as a buffer to stabilize our genome and silence repetitive chromosomic regions. Many diseases show an alteration of DNA methylation that disrupts cellular activity.” Esteller’s research mainly focuses on alterations in DNA methylation, histone modifications and chromatin in human cancer. At present, he is working on establishing epigenome and epitranscriptome maps for normal and transformed cells.

In mammals, methylation is mostly sparse but is globally distributed in specific CpG or CG (cytosine–guanine) sequences. In certain regions of the genome, CpG is abundantly found (e.g., CpG islands). In healthy cells, CpG islands associated with gene promotors are typically free from methylation, whereas islands found within gene bodies tend to become methylated during development. Researchers have pointed out that methylation of CpG islands at promotor regions can cause inappropriate downregulation of specific genes (e.g., silencing of tumor suppressor genes in cancer cells). 

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