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Metilasi DNA melibatkan penambahan gugus metil pada posisi 5 dari cincin pirimidin sitosin atau jumlah
6 nitrogen purin adenin cincin (sitosin dan adenin adalah dua dari empat basa DNA).
Modifikasi ini bisa diwariskan melalui pembelahan sel. Metilasi DNA biasanya dihapus selama
pembentukan zigot dan re-dibentuk melalui pembelahan sel yang berurutan selama pengembangan
meskipun penelitian terbaru menunjukkan bahwa kelompok metil hidroksilasi terjadi bukan penghapusan
lengkap dari kelompok metil zigot.
Metilasi DNA adalah bagian penting dari perkembangan organisme normal dan diferensiasi selular pada
organisme yang lebih tinggi. Metilasi DNA stabil mengubah pola ekspresi gen dalam sel sehingga sel
dapat "ingat di mana mereka telah" atau mengurangi ekspresi gen, misalnya, sel-sel diprogram untuk
menjadi pulau pankreas selama perkembangan embrio tetap pankreas pulau sepanjang kehidupan
organisme tanpa sinyal terus mengatakan kepada mereka bahwa mereka harus tetap pulau.
Selain itu, metilasi DNA menekan ekspresi gen virus dan elemen merusak lainnya yang telah dimasukkan
ke dalam genom host dari waktu ke waktu.
Metilasi DNA juga membentuk dasar struktur kromatin, yang memungkinkan sel untuk membentuk
karakteristik segudang penting bagi kehidupan multiselular dari urutan berubah tunggal DNA.
Metilasi DNA juga memainkan peran penting dalam pengembangan hampir semua jenis kanker.
Metilasi DNA melibatkan penambahan grup metil untuk DNA - misalnya, untuk karbon 5 jumlah cincin
pirimidin sitosin - dalam hal ini dengan efek spesifik mengurangi ekspresi gen. Metilasi DNA pada posisi 5
dari sitosin telah ditemukan di setiap vertebrata diperiksa. Dalam jaringan dewasa somatik, metilasi DNA
biasanya terjadi dalam konteks dinukleotida CpG; non-CpG metilasi adalah lazim dalam sel batang
embrio.
Metilasi merupakan reaksi organik yang menambahkan gugus metil pada molekul substrat. Metilasi merupakan salah satu bentuk alkilasi
Definisi Metilasi DNA:
jenis kimia modifi kasi yang melibatkan penambahan metil kelompok pada karbon-5 dari sitosin pirimidin cincin. Ini modifi kasi menghambat transkripsiinisiasi dan telah terlibat dalam menghambat sel pertumbuhan dan diferensiasi . Ini telah menghasilkan tes DNA ing metil trans ferase inhibitorsebagai anti kanker agen dan diferensiasi agen s.
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 hydrogenatom. 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 ofgene expression, regulation of protein function, 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 histological staining artifacts.
Epigenetics
Methylation contributing to epigenetic inheritance can occur through either 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 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 (made up of about 65% CG residues),
wherein none are 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.[1] 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-studied in the histones. The transfer of methyl groups fromS-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.[2][3] Protein methylation is one
type of post-translational modification.
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 hypermethylationand an increase in expression of DNA methyltransferase.
[14] 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.[15] 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 (GSTP1) appears to be a promising diagnostic indicator of prostate cancer.[16]
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.[17]
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 (which are not methylated in this manner) 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 (RFLP) testing, used to
detect DNA polymorphisms.