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DNA methylation is a process by which methyl groups are added to DNA. Methylation modifies the function of the DNA. 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 repetitive elements, and carcinogenesis. Two of DNA's four nucleotides, cytosine and adenine, can be methylated. Adenine methylation is restricted to prokaryotes.The rate of cytosine DNA methylation differs strongly between species: 14% of cytosines are methylated in ''Arabidopsis thaliana'', 4% in ''Mus musculus'', 2.3% in ''Escherichia coli'', 0.03% in ''Drosophila'', and virtually none (< 0.0002%) in yeast species. DNA methylation can stably alter the expression of genes in cells as cells divide and differentiate from embryonic stem cells into specific tissues. The resulting change is normally permanent and unidirectional, preventing a cell from reverting to a stem cell or converting into a different cell type. However, DNA methylation can be removed either passively, by dilution as cells divide, or by a faster, active, process. The latter process occurs via hydroxylation of the methyl groups that are to be removed, rather than by complete removal of methyl groups. DNA methylation is typically removed during zygote formation and re-established through successive cell divisions during development. Methylation modifications that regulate gene expression are usually heritable through mitotic cell division; some methylation is also heritable through the specialized meiotic cell division that creates egg and sperm cells, resulting in genomic imprinting. DNA methylation suppresses the expression of endogenous retroviral genes and other harmful stretches of DNA that have been incorporated into the host genome over time. DNA methylation also forms the basis of chromatin structure, which enables a single cell to grow into multiple organs or perform multiple functions. DNA methylation also plays a crucial role in the development of nearly all types of cancer. DNA methylation at the 5 position of cytosine has the specific effect of reducing gene expression and has been found in every vertebrate examined. In adult somatic cells (cells in the body, not used for reproduction), DNA methylation typically occurs in a CpG dinucleotide context; non-CpG methylation is prevalent in embryonic stem cells, and has also been indicated in neural development. ==In mammals== :''For significant overlapping coverage, see also Methylation.'' Between 60% and 90% of all CpGs are methylated in mammals. Methylated C residues spontaneously deaminate to form T residues over time; hence CpG dinucleotides steadily deaminate to TpG dinucleotides, which is evidenced by the under-representation of CpG dinucleotides in the human genome (they occur at only 21% of the expected frequency). (On the other hand, spontaneous deamination of unmethylated C residues gives rise to U residues, a change that is quickly recognized and repaired by the cell.) DNA methylation has been noted to target different organisms in different areas, and have varying functions. For example, the pattern of DNA methylation in mammals is generally evenly distributed throughout CpG sites (with exceptions). However, invertebrates experience the opposite: CpG methylation patterns that are grouped in clusters. Unmethylated CpGs are often grouped in clusters called ''CpG islands'', which are present in the 5' regulatory regions of many genes. In many disease processes, such as cancer, gene promoter CpG islands acquire abnormal hypermethylation, which results in transcriptional silencing that can be inherited by daughter cells following cell division. Alterations of DNA methylation have been recognized as an important component of cancer development. Hypomethylation, in general, arises earlier and is linked to chromosomal instability and loss of imprinting, whereas hypermethylation is associated with promoters and can arise secondary to gene (oncogene suppressor) silencing, but might be a target for epigenetic therapy. DNA methylation may affect the transcription of genes in two ways. First, the methylation of DNA itself may physically impede the binding of transcriptional proteins to the gene, and second, and likely more important, methylated DNA may be bound by proteins known as methyl-CpG-binding domain proteins (MBDs). MBD proteins then recruit additional proteins to the locus, such as histone deacetylases and other chromatin remodeling proteins that can modify histones, thereby forming compact, inactive chromatin, termed heterochromatin. This link between DNA methylation and chromatin structure is very important. In particular, loss of methyl-CpG-binding protein 2 (MeCP2) has been implicated in Rett syndrome; and methyl-CpG-binding domain protein 2 (MBD2) mediates the transcriptional silencing of hypermethylated genes in cancer. Research has suggested that long-term memory storage in humans may be regulated by DNA methylation. DNA methylation levels can be used to estimate age, forming an accurate biological clock in humans and chimpanzees. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「DNA methylation」の詳細全文を読む スポンサード リンク
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