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  • In the chemical sciences, methylation denotes the addition of a methyl group to a substrate

  • or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation

  • with a methyl group, rather than a larger carbon chain, replacing a hydrogen atom. These

  • terms are commonly used in chemistry, biochemistry, soil science, and the biological sciences.

  • In biological systems, methylation is catalyzed by enzymes; such methylation can be involved

  • in modification of heavy metals, regulation of gene expression, regulation of protein

  • function, and RNA processing. Methylation of heavy metals can also occur outside of

  • biological systems. Chemical methylation of tissue samples is also one method for reducing

  • certain histological staining artifacts.

  • In biology Epigenetics

  • Methylation contributing to epigenetic inheritance can occur through either DNA methylation or

  • protein methylation. DNA methylation in vertebrates typically occurs

  • at CpG sites. This methylation results in the conversion of the cytosine to 5-methylcytosine.

  • The formation of Me-CpG is catalyzed by the enzyme DNA methyltransferase. Human DNA has

  • about 80–90% of CpG sites methylated, but there are certain areas, known as CpG islands,

  • that are GC-rich, wherein none is methylated. These are associated with the promoters of

  • 56% of mammalian genes, including all ubiquitously expressed genes. One to two percent of the

  • human genome are CpG clusters, and there is an inverse relationship between CpG methylation

  • and transcriptional activity. Protein methylation typically takes place

  • on arginine or lysine amino acid residues in the protein sequence. Arginine can be methylated

  • once or twice, with either both methyl groups on one terminal nitrogen or one on both nitrogens

  • by peptidylarginine methyltransferases. Lysine can be methylated once, twice or three times

  • by lysine methyltransferases. Protein methylation has been most studied in the histones. The

  • transfer of methyl groups from S-adenosyl methionine to histones is catalyzed by enzymes

  • known as histone methyltransferases. Histones that are methylated on certain residues can

  • act epigenetically to repress or activate gene expression. Protein methylation is one

  • type of post-translational modification. Embryonic development

  • While chromosomes in the somatic cells retain the parental methylation patterns, during

  • the development of germ cells their genomes are demethylated. After that, a De novo methylation

  • of the germ cells occurs, modifying and adding epigenetic information to the genome based

  • on the sex of the individual. After fertilization of an oocyte and formations

  • of a zygote, its combined genome is demethylated and remethylated again. By blastula stage,

  • the methylation of the embryonic cells is complete.

  • The process of demethylation/remethylation is referred to as "reprogramming". The importance

  • of methylation was shown in knockout mutants without DNA methyltransferase, which all died

  • at the morula stage. 5-methylcytosine conversion to 5-hydroxymethylcytosine

  • is sometimes associated with labile, unstable nucleosomes which are frequently repositioned

  • during stem cell differentiation. Postnatal development

  • Increasing evidence is revealing a role of methylation in the interaction of environmental

  • factors with genetic expression. Differences in maternal care during the first 6 days of

  • life in the rat induce differential methylation patterns in some promoter regions, thus influencing

  • gene expression. Furthermore, processes that are even more dynamic, such as interleukin

  • signaling, have been shown to be regulated by methylation.

  • Research in humans has shown that repeated high level activation of the body's stress

  • system, especially in early childhood, can alter methylation processes and lead to changes

  • in the chemistry of the individual's DNA. The chemical changes can disable genes and

  • prevent the brain from properly regulating its response to stress. Researchers and clinicians

  • have drawn a link between this neurochemical dysregulation and the development of chronic

  • health problems such as depression, obesity, diabetes, hypertension, and coronary artery

  • disease. Cancer

  • The pattern of methylation has recently become an important topic for research. Studies have

  • found that in normal tissue, methylation of a gene is mainly localized to the coding region,

  • which is CpG-poor. In contrast, the promoter region of the gene is unmethylated, despite

  • a high density of CpG islands in the region. Neoplasia is characterized by "methylation

  • imbalance" where genome-wide hypomethylation is accompanied by localized hypermethylation

  • and an increase in expression of DNA methyltransferase. Typically, there is hypermethylation of tumor

  • suppressor genes and hypomethylation of oncogenes. The overall methylation state in a cell might

  • also be a precipitating factor in carcinogenesis as evidence suggests that genome-wide hypomethylation

  • can lead to chromosome instability and increased mutation rates. The methylation state of some

  • genes can be used as a biomarker for tumorigenesis. For instance, hypermethylation of the pi-class

  • glutathione S-transferase gene appears to be a promising diagnostic indicator of prostate

  • cancer. In cancer, the dynamics of genetic and epigenetic

  • gene silencing are very different. Somatic genetic mutation leads to a block in the production

  • of functional protein from the mutant allele. If a selective advantage is conferred to the

  • cell, the cells expand clonally to give rise to a tumor in which all cells lack the capacity

  • to produce protein. In contrast, epigenetically mediated gene silencing occurs gradually.

  • It begins with a subtle decrease in transcription, fostering a decrease in protection of the

  • CpG island from the spread of flanking heterochromatin and methylation into the island. This loss

  • results in gradual increases of individual CpG sites, which vary between copies of the

  • same gene in different cells. Bacterial host defense

  • In addition, adenosine or cytosine methylation is part of the restriction modification system

  • of many bacteria. Bacterial DNAs are methylated periodically throughout the genome. A methylase

  • is the enzyme that recognizes a specific sequence and methylates one of the bases in or near

  • that sequence. Foreign DNAs that are introduced into the cell are degraded by sequence-specific

  • restriction enzymes. Bacterial genomic DNA is not recognized by these restriction enzymes.

  • The methylation of native DNA acts as a sort of primitive immune system, allowing the bacteria

  • to protect themselves from infection by bacteriophage. These restriction enzymes are the basis of

  • restriction fragment length polymorphism testing, used to detect DNA polymorphisms.

  • Application in Prenatal Diagnosis Recent prenatal diagnostic techniques analyse

  • cell-free fetal DNA found in maternal blood; however, ffDNA is found in very small amounts

  • and is difficult to distinguish from a majority of maternal cell-free DNA. Specific regions

  • of the genome have been found that are differentially methylated when comparing fetal DNA with maternal

  • DNA. For example, the AIRE gene promoter has been found to be highly methylated in fetal

  • DNA but under-methylated in maternal DNA. Methylated DNA immunoprecipitation has been

  • utilized to purify ffDNA from maternal serum for the purpose of pre-natal diagnosis of

  • Down syndrome. In chemistry

  • The term methylation in organic chemistry refers to the alkylation process used to describe

  • the delivery of a CH3 group. This is commonly performed using electrophilic methyl sources

  • iodomethane, dimethyl sulfate, dimethyl carbonate, or less commonly with the more

  • powerful methylating reagents of methyl triflate, diazomethane or methyl fluorosulfonate, which

  • all react via SN2 nucleophilic substitution. For example a carboxylate may be methylated

  • on oxygen to give a methyl ester, an alkoxide salt ROmay be likewise methylated to give

  • an ether, ROCH3, or a ketone enolate may be methylated on carbon to produce a new ketone.

  • On the other hand, the methylation may involve use of nucleophilic methyl compounds such

  • as methyllithium or Grignard reagents. For example, CH3Li will methylate acetone, adding

  • across the carbonyl to give the lithium alkoxide of tert-butanol:

  • Purdie methylation Purdie methylation is a specific method for

  • the methylation at oxygen of carbohydrates using iodomethane and silver oxide.

  • 5-O-Methylations 5-O-Methylgenistein

  • 5-O-Methylmyricetin 5-O-Methylquercetin, also known as azaleatin

  • See also alkylation

  • Bisulfite sequencingthe biochemical method used to determine the presence or absence

  • of methyl groups on a DNA sequence MethDB DNA Methylation Database

  • Microscale thermophoresis – a biophysical method to determine the methylisation state

  • of DNA References

  • External links deltaMasses Detection of Methylations after

  • Mass Spectrometry

In the chemical sciences, methylation denotes the addition of a methyl group to a substrate

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C1 高級 英國腔

甲基化 (Methylation)

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    wehou 發佈於 2021 年 01 月 14 日
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