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Methylation is a term used in the chemical sciences to denote the attachment or substitution of a
methyl on various Substrate_%28chemistry%29. This term is commonly used in chemistry, biochemistry, and the biological sciences.
In biochemistry, methylation more specifically refers to the replacement of a Hydrogen#Compounds atom with the methyl group.
In biological systems, methylation is Catalysis by enzymes; such methylation can be involved in modification of
heavy metals, regulation of
gene expression, regulation of Protein#Functions, and
RNA metabolism. Methylation of
heavy metals can also occur outside of biological systems. Chemical methylation of tissue samples is also one method for reducing certain Histology#Histological Artifacts.
Biological methylation
Epigenetics
Methylation contributing to epigenetic inheritance can occur either through DNA methylation or protein methylation.
DNA methylation in vertebrates typically occurs at
CpG sites (cytosine-phosphate-guanine sites; that is, where a cytosine is directly followed by a guanine in the DNA sequence); this methylation results in the conversion of the cytosine to
5-methylcytosine. The formation of Me-CpG is
Catalysis by the enzyme DNA methyltransferase. CpG sites are uncommon in vertebrate genomes but are often found at higher density near vertebrate
gene promoters where they are collectively referred to as CpG islands. The methylation state of these CpG sites can have a major impact on gene expression.
Protein methylation typically takes place on
arginine or
lysine amino acid residues in the protein sequence. Arginine can be methylated once (monomethylated arginine) or twice, with either both methyl groups on one terminal nitrogen (asymmetric dimethylated arginine) or one on both nitrogens (symmetric dimethylated arginine) by
peptidylarginine methyltransferases (PRMTs). Lysine can be methylated once, twice or three times by
lysine methyltransferases. Protein methylation has been most well studied in the
histones. The transfer of
methyl groups from S-adenosyl methionine to histones is catalyzed by enzymes known as
histone methyltransferases. Histones which are methylated on certain residues can act Epigenetics to repress or activate "gene" expression. Protein methylation is one type of
post-translational modification.
Embryonic development
In early development (
fertilization to
8-cell stage), the eukaryotic genome is
demethylation. From the 8-cell stage to the
morula,
de novo methylation of the genome occurs, modifying and adding epigenetic information to the genome. By blastula stage, the methylation is complete. This process is referred to as "epigenetic reprogramming". The importance of methylation was shown in
gene knockout mutants without DNA methyltransferase. All the resulting
embryos died at the morula stage.
Methylation in 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 and thus influencing gene expression (). Furthermore, even more dynamic processes such as
interleukin signaling have been shown to be regulated by methylation ().
Methylation and 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 localised 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 wiktionary:hypomethylation is accompanied by localized wiktionary:hypermethylation and an increase in gene expression of
DNA methyltransferase (1). 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 (3). The methylation state of some genes can be used as a wiktionary:biomarker for
wiktionary:tumorigenesis. For instance, hypermethylation of the pi-class glutathione S-transferase gene (GSTP1) appears to be a promising
diagnostic indicator of
prostate cancer (2).
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 (6).
Methylation and bacterial host defense
Additionally,
adenosine or cytosine methylation is part of the
restriction modification system of many
bacterium. 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 (which are not methylated in this manner) that are introduced into the
cell (biology) 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 or
phage. These restriction enzymes are the basis of restriction fragment length polymorphism (RFLP) testing. With this technique, geneticists use various bacterial restriction endonucleases (restriction enzymes) to split DNA at specific sites in order to detect DNA
Polymorphism (biology), useful for genetic fingerprinting and genetic engineering.
Methylation 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
electrophile methyl sources -
iodomethane, dimethyl sulfate,
dimethyl carbonate, or less commonly with the more powerful (and more dangerous) methylating reagents of
methyl triflate or methyl fluorosulfonate (magic methyl), which all react via SN2 nucleophilic substitution. For example a carboxylate may be methylated on oxygen to give a methyl
ester, an
alkoxide salt RO− may be likewise methylated to give an
ether, ROCH3, or a ketone enolate may be methylated on carbon to produce a new ketone.
salt and a phenol using iodomethane
Alternatively, the methylation may involve use of nucleophile methyl compounds such as organolithium reagent (CH3Li) or
Grignard reagents (CH3MgX). For example, CH3Li will methylate acetone, adding across the carbonyl (C=O) to give the lithium alkoxide of butanol:
by
methyl lithium
References
March, J.; Advanced Organic Chemistry, 5th ed., Wiley, New York, 2001.
External links
- http://www.methdb.de/ DNA Methylation Database
- deltaMasses Detection of Methylations after Mass Spectrometry
Methylation is a term used in the chemical sciences to denote the attachment or substitution of a
methyl on various
Substrate_%28chemistry%29. This term is commonly used in chemistry,
biochemistry, and the biological sciences.
In biochemistry, methylation more specifically refers to the replacement of a
Hydrogen#Compounds atom with the methyl group.
In biological systems, methylation is Catalysis by enzymes; such methylation can be involved in modification of
heavy metals, regulation of
gene expression, regulation of
Protein#Functions, and
RNA metabolism. Methylation of heavy metals can also occur outside of biological systems. Chemical methylation of tissue samples is also one method for reducing certain
Histology#Histological Artifacts.
Biological methylation
Epigenetics
Methylation contributing to epigenetic inheritance can occur either through DNA methylation or protein methylation.
DNA methylation in vertebrates typically occurs at
CpG sites (cytosine-phosphate-guanine sites; that is, where a cytosine is directly followed by a guanine in the DNA sequence); this methylation results in the conversion of the cytosine to
5-methylcytosine. The formation of Me-CpG is
Catalysis by the enzyme DNA methyltransferase. CpG sites are uncommon in vertebrate genomes but are often found at higher density near vertebrate
gene promoters where they are collectively referred to as
CpG islands. The methylation state of these CpG sites can have a major impact on
gene expression.
Protein methylation typically takes place on arginine or
lysine amino acid residues in the protein sequence. Arginine can be methylated once (monomethylated arginine) or twice, with either both methyl groups on one terminal nitrogen (asymmetric dimethylated arginine) or one on both nitrogens (symmetric dimethylated arginine) by peptidylarginine methyltransferases (PRMTs). Lysine can be methylated once, twice or three times by
lysine methyltransferases. Protein methylation has been most well studied in the
histones. The transfer of
methyl groups from
S-adenosyl methionine to histones is catalyzed by enzymes known as
histone methyltransferases. Histones which are methylated on certain residues can act Epigenetics to repress or activate "gene" expression. Protein methylation is one type of post-translational modification.
Embryonic development
In early development (
fertilization to
8-cell stage), the eukaryotic genome is
demethylation. From the 8-cell stage to the
morula,
de novo methylation of the genome occurs, modifying and adding epigenetic information to the genome. By blastula stage, the methylation is complete. This process is referred to as "
epigenetic reprogramming". The importance of methylation was shown in gene knockout mutants without DNA methyltransferase. All the resulting embryos died at the morula stage.
Methylation in 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 and thus influencing gene expression (). Furthermore, even more dynamic processes such as interleukin signaling have been shown to be regulated by methylation ().
Methylation and 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 localised 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 wiktionary:hypomethylation is accompanied by localized
wiktionary:hypermethylation and an increase in
gene expression of DNA methyltransferase (1). 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 (3). The methylation state of some genes can be used as a
wiktionary:biomarker for
wiktionary:tumorigenesis. For instance, hypermethylation of the pi-class glutathione S-transferase gene (GSTP1) appears to be a promising
diagnostic indicator of prostate cancer (2).
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 (6).
Methylation and bacterial host defense
Additionally,
adenosine or
cytosine methylation is part of the restriction modification system of many bacterium. 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 (which are not methylated in this manner) that are introduced into the
cell (biology) 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 or
phage. These restriction enzymes are the basis of
restriction fragment length polymorphism (RFLP) testing. With this technique, geneticists use various bacterial restriction
endonucleases (restriction enzymes) to split DNA at specific sites in order to detect DNA Polymorphism (biology), useful for genetic fingerprinting and genetic engineering.
Methylation 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
electrophile methyl sources - iodomethane,
dimethyl sulfate,
dimethyl carbonate, or less commonly with the more powerful (and more dangerous) methylating reagents of
methyl triflate or methyl fluorosulfonate (magic methyl), which all react via SN2 nucleophilic substitution. For example a
carboxylate may be methylated on oxygen to give a methyl
ester, an
alkoxide salt RO− may be likewise methylated to give an ether, ROCH3, or a ketone
enolate may be methylated on carbon to produce a new
ketone.
salt and a
phenol using
iodomethaneAlternatively, the methylation may involve use of nucleophile methyl compounds such as
organolithium reagent (CH3Li) or
Grignard reagents (CH3MgX). For example, CH3Li will methylate
acetone, adding across the carbonyl (
C=O) to give the lithium alkoxide of butanol:
by
methyl lithium
References
March, J.; Advanced Organic Chemistry, 5th ed., Wiley, New York, 2001.
External links
- http://www.methdb.de/ DNA Methylation Database
- deltaMasses Detection of Methylations after Mass Spectrometry
Methylation - Wikipedia, the free encyclopedia
Methylation is a term used in the chemical sciences to denote the attachment or substitution of a methyl group on various substrates. This term is commonly used in chemistry, ...
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DNA methylation - Wikipedia, the free encyclopedia
DNA methylation is a type of chemical modification of DNA that can be inherited and subsequently removed without changing the original DNA sequence.
The Methylation Cycle | Dr Myhill
The Methylation Cycle: August 2007 Chronic Fatigue Syndrome is a symptom, not a diagnosis, and the name of the game is to identify the underlying causes.
Methylation
Methylation. A methyl group consists of one carbon and three hydrogen atoms. Methyl groups are used by many organisms to modify DNA, RNA or proteins.
txt001gsb: Aberrant DNA methylation in cancer: potential clinical ...
Expert Reviews in Molecular Medicine: http://www.expertreviews.org/ Accession information: (02)00422-2h.htm (shortcode: txt001gsb); 4 March 2002
About Gender - Methylation
The following illustrates methylation of cytidine where H is replaced by CH3
Cancer Research UK | CancerHelp UK | A study to see if cell changes ...
A study to see if cell changes can help doctors tell who will respond well to chemotherapy for ovarian cancer (DNA methylation study) This study will look at cell changes in women ...
Dna Methylation Study
NB: The information displayed below does not replace the protocol. The latest protocol version should always be consulted before making clinical decisions.