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5-Methylcytosine
Encyclopedia
5-Methylcytosine is a methylated
form of the DNA
base cytosine
that may be involved in the regulation of gene transcription
. When cytosine is methylated, the DNA maintains the same sequence, but the expression of methylated genes
can be altered (the study of this is called epigenetics
).
In the figure on the right, a methyl group
, is attached to the 5th carbon atom (counting counterclockwise from the NH nitrogen
). This methyl group distinguishes 5-methylcytosine from cytosine.
formed by the action of DNA methyltransferase
s.
The function of this chemical varies significantly among species:
While spontaneous deamination
of cytosine forms uracil
, which is recognized and removed by DNA repair enzymes, deamination of 5-methylcytosine forms thymine
. This conversion of a DNA base from cytosine (C) to thymine (T) can result in a transition mutation
. In addition, active enzymatic deamination of cytosine or 5-methylcytosine by the APOBEC
family of cytosine deaminases could have beneficial implications on various cellular processes as well as on organismal evolution. The implications of deamination on 5-hydroxymethylcytosine, on the other hand, remains less understood.
with use of reagents such as nitrous acid
; cytosine deaminates to uracil under similar conditions.
5-Methylcytosine is resistant to deamination by bisulfite
treatment, which deaminates cytosine residues. This property is often exploited to analyze DNA cytosine methylation patterns with bisulfite sequencing
.
)
Methylation
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, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
form of the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
base cytosine
Cytosine
Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...
that may be involved in the regulation of gene transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
. When cytosine is methylated, the DNA maintains the same sequence, but the expression of methylated genes
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
can be altered (the study of this is called epigenetics
Epigenetics
In biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- -genetics...
).
In the figure on the right, a methyl group
Methyl group
Methyl group is a functional group derived from methane, containing one carbon atom bonded to three hydrogen atoms —CH3. The group is often abbreviated Me. Such hydrocarbon groups occur in many organic compounds. The methyl group can be found in three forms: anion, cation and radical. The anion...
, is attached to the 5th carbon atom (counting counterclockwise from the NH nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
). This methyl group distinguishes 5-methylcytosine from cytosine.
In vivo
5-Methylcytosine is an epigenetic modificationEpigenetics
In biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- -genetics...
formed by the action of DNA methyltransferase
DNA methyltransferase
In biochemistry, the DNA methyltransferase family of enzymescatalyze the transfer of a methyl group to DNA. DNA methylation serves a wide variety of biological functions...
s.
The function of this chemical varies significantly among species:
- In bacteriaBacteriaBacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, 5-methylcytosine can be found at a variety of sites, and is often used as a marker to protect DNA from being cut by native methylation-sensitive restriction enzymes. - In plants, 5-methylcytosine occurs at CpGCpG siteCpG sites or CG sites are regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence of bases along its length. "CpG" is shorthand for "—C—phosphate—G—", that is, cytosine and guanine separated by only one phosphate; phosphate links any two nucleosides...
, CpHpG and CpHpH sequences (where H = A, C or T). - In fungi and animals, 5-methylcytosine predominantly occurs at CpGCpG siteCpG sites or CG sites are regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence of bases along its length. "CpG" is shorthand for "—C—phosphate—G—", that is, cytosine and guanine separated by only one phosphate; phosphate links any two nucleosides...
dinucleotides. Most eukaryoteEukaryoteA eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s methylate only a small percentage of these sites, but 70-80% of CpG cytosines are methylated in vertebrateVertebrateVertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
s.
While spontaneous deamination
Deamination
Deamination is the removal of an amine group from a molecule. Enzymes which catalyse this reaction are called deaminases.In the human body, deamination takes place primarily in the liver, however glutamate is also deaminated in the kidneys. Deamination is the process by which amino acids are...
of cytosine forms uracil
Uracil
Uracil is one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others are adenine, cytosine, and guanine. In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine.Uracil is a common and...
, which is recognized and removed by DNA repair enzymes, deamination of 5-methylcytosine forms thymine
Thymine
Thymine is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at...
. This conversion of a DNA base from cytosine (C) to thymine (T) can result in a transition mutation
Transition (genetics)
In genetics, a transition is a point mutation that changes a purine nucleotide to another purine or a pyrimidine nucleotide to another pyrimidine . Approximately two out of three single nucleotide polymorphisms are transitions....
. In addition, active enzymatic deamination of cytosine or 5-methylcytosine by the APOBEC
APOBEC
300px|thumb|upright|alt = Colored dice with checkered background|Example of a member of the APOBEC family, APOBEC-2. A cytidine deaminase from Homo Sapiens....
family of cytosine deaminases could have beneficial implications on various cellular processes as well as on organismal evolution. The implications of deamination on 5-hydroxymethylcytosine, on the other hand, remains less understood.
In vitro
The NH2 group can be removed (deamination) from 5-Methylcytosine to form thymineThymine
Thymine is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at...
with use of reagents such as nitrous acid
Nitrous acid
Nitrous acid is a weak and monobasic acid known only in solution and in the form of nitrite salts.Nitrous acid is used to make diazides from amines; this occurs by nucleophilic attack of the amine onto the nitrite, reprotonation by the surrounding solvent, and double-elimination of water...
; cytosine deaminates to uracil under similar conditions.
5-Methylcytosine is resistant to deamination by bisulfite
Bisulfite
Bisulfite ion is the ion HSO3−. Salts containing the HSO3− ion are termed bisulfites also known as sulfite lyes...
treatment, which deaminates cytosine residues. This property is often exploited to analyze DNA cytosine methylation patterns with bisulfite sequencing
Bisulfite sequencing
Bisulfite sequencing is the use of bisulfite treatment of DNA to determine its pattern of methylation. DNA methylation was the first discovered epigenetic mark, and remains the most studied...
.
Literature
(available online at the United States National Center for Biotechnology InformationNational Center for Biotechnology Information
The National Center for Biotechnology Information is part of the United States National Library of Medicine , a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988 through legislation sponsored by Senator Claude Pepper...
)