DNA Methylation
Introduction
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging and carcinogenesis.
Biochemistry of DNA Methylation
DNA methylation involves the addition of a methyl group to the DNA molecule. This occurs at the carbon 5 position of the cytosine pyrimidine ring. This reaction is catalyzed by the enzyme DNA methyltransferase. The most widely characterized DNA methyltransferases are DNMT1, DNMT3A, and DNMT3B. DNMT1 is the most abundant methyltransferase in mammalian cells and is primarily responsible for copying DNA methylation patterns to the daughter strands during DNA replication.
Function of DNA Methylation
DNA methylation serves a wide variety of biological functions. All mammalian cells apart from germ cells and stem cells are subject to DNA methylation. The functions of DNA methylation include gene regulation, genomic imprinting, X-chromosome inactivation, suppression of repetitive elements, and carcinogenesis.
Gene Regulation
DNA methylation plays a crucial role in gene regulation. In general, high levels of methylation in the promoter region of a gene represses gene transcription, while lower levels of methylation in the body of a gene increases gene expression.
Genomic Imprinting
Genomic imprinting is an epigenetic process by which certain genes are expressed in a parent-of-origin-specific manner. DNA methylation is thought to play a crucial role in genomic imprinting, with differential methylation occurring on the maternal and paternal alleles.
X-Chromosome Inactivation
DNA methylation has been implicated in X-chromosome inactivation in female mammals. X-chromosome inactivation is the process by which one of the two copies of the X chromosome present in female mammals is inactivated to dosage compensate for the double genetic dose compared with males.
Suppression of Repetitive Elements
Repetitive elements, such as transposable elements, make up a large proportion of the mammalian genome. DNA methylation plays a key role in suppressing these elements, preventing them from causing harmful mutations and maintaining genome stability.
Carcinogenesis
Aberrant DNA methylation patterns are a hallmark of cancer and can lead to the silencing of tumor suppressor genes. Many types of cancer show a general hypomethylation of the genome combined with hypermethylation of specific genes.
DNA Methylation and Disease
Abnormal DNA methylation patterns have been linked to a number of diseases, including cancer, autoimmune diseases, and neurological disorders. In cancer, DNA methylation patterns can be used as biomarkers for early detection, prognosis, and treatment response.
DNA Methylation and Aging
DNA methylation is also associated with aging. The methylation pattern of an individual's genome changes as they age and this "methylation clock" can be used to predict biological age.