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Encyclopedia > DNA methylation

DNA methylation is a type of chemical modification of DNA that can be inherited without changing the DNA sequence. As such, it is part of the epigenetic code and is the most characterized epigenetic mechanism. The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ... The epigenetic code is hypothesized to be a defining code in every eukaryotic cell consisting of the specific epigenetic modification in each cell. ... In Biology, while the subject of genetics focuses on how organisms can inherit traits by inheriting genes from their parent(s), which encode information for cell function as sequences of DNA, epigenetics is sometimes used to refer to additional methods of biological inheritance that do not directly relate to the...


DNA methylation involves the addition of a methyl group to DNA — for example, to the number 5 carbon of the cytosine pyrimidine ring. In chemistry a methyl-group is a hydrophobic Alkyl functional group which is derived from methane (CH4). ... Cytosine is one of the 5 main nucleobases used in storing and transporting genetic information within a cell in the nucleic acids DNA and RNA. It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached (an amine group at position 4 and a keto group at...


DNA methylation is probably universal in eukaryotes. In humans, approximately 1% of DNA bases undergo DNA methylation. In adult somatic tissues, DNA methylation typically occurs in a CpG dinucleotide context; non-CpG methylation is prevalent in embryonic stem cells.[1] [2] A group of organisms is said to have common descent if they have a common ancestor. ... Kingdoms Eukaryotes are organisms with complex cells, in which the genetic material is organized into membrane-bound nuclei. ... Human beings are defined variously in biological, spiritual, and cultural terms, or in combinations thereof. ... The term somatic refers to the body, as distinct from some other entity, such as the mind. ... CpG sites are regions of the DNA where a cytosine nucleotide is situated next to a guanine nucleotide. ... Mouse embryonic stem cells with fluorescent marker. ...


In plants, cytosines are methylated both symmetrically (CpG or CpNpG) and asymmetrically (CpNpNp), where N can be any nucleotide.


The methylation status of specific cytosines can be determined using methods based on bisulfite sequencing. Figure 1: Outline of bisulfite conversion of sample sequence of genomic DNA. Nucleotides in blue are unmethylated cytosines converted to uracils by bisulfite, while red nucleotides are 5-methylcytosines resistant to conversion. ...

Contents

DNA methylation in mammals

Between 60-70% of all CpGs are methylated. Unmethylated CpGs are grouped in clusters called "CpG islands" that 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 heritable transcriptional silencing. DNA methylation may impact the transcription of genes in two ways. First, the methylation of DNA may itself physically impede the binding of transcriptional proteins to the gene, thus blocking transcription. 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 remodelling proteins that can modify histones, thereby forming compact, inactive chromatin termed silent chromatin. 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. CpG islands are small stretches of DNA rich in CG doublets found near the 5 regions of some genes. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ... CpG islands are regions of DNA near and in the promoter of a mammalian gene where a large concentration of phosphodiester-linked cytosine and guanine pairs exist. ... Histone deacetylases (HDAC) are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. ... Rett syndrome is a neurodevelopmental disorder that is classified as a pervasive developmental disorder by the DSM-IV. Many argue that this is a mis-classification just as it would be to include such disorders as fragile X syndrome, tuberous sclerosis, or Down syndrome where one can see autistic features. ...


DNA methylation in humans

In humans, the process of DNA methylation is carried out by three enzymes, DNA methyltransferase 1, 3a, and 3b (DNMT1, DNMT3a, DNMT3b). It is thought that DNMT3a and DNMT3b are the de novo methyltransferases that set up DNA methylation patterns early in development. DNMT1 is the proposed maintenance methyltransferase that is responsible for copying DNA methylation patterns to the daughter strands during DNA replication. DNMT3L is a protein that is homologous to the other DNMT3s but has no catalytic activity. Instead, DNMT3L assists the de novo methyltransferases by increasing their ability to bind to DNA and stimulating their activity. Finally, DNMT2 has been identified as an "enigmatic" DNA methyltransferase homolog, containing all 10 sequence motifs common to all DNA methyltransferases; however, DNMT2 does not methylate DNA but instead methylates a small RNA. DNA methyltransferase is an enzyme whose function is to catalyze the transfer of methyl groups between molecules, in this case, DNA. There are two main types of methyltransferases, de novo and maintenance. ...


Since many tumor suppressor genes are silenced by DNA methylation during carcinogenesis, there have been attempts to re-express these genes by inhibiting the DNMTs. 5-aza-2'-deoxycytidine (decitabine) is a nucleoside analog that inhibits DNMTs by trapping them in a covalent complex on DNA by preventing the β-elimination step of catalysis, thus resulting in the enzymes' degradation. However, for decitabine to be active, it must be incorporated into the genome of the cell, but this can cause mutations in the daughter cells if the cell does not die. Additionally, decitabine is toxic to the bone marrow, which limits the size of its therapeutic window. These pitfalls have led to the development of antisense RNA therapies that target the DNMTs by degrading their mRNAs and preventing their translation. However, it is currently unclear if targeting DNMT1 alone is sufficient to reactivate tumor suppressor genes silenced by DNA methylation. Cancers are caused by a series of mutations. ... Decitabine (Dacogen®), or 5-aza-2-deoxy-cytidine, is indicated for treatment of patients with myelodysplastic syndrome (MDS), including previously treated and untreated, de novo, and secondary MDS of all FAB subtypes and Intermediate-1, Intermediate-2, and High-Risk IPSS groups. ... A base analog is a chemical that can substitute a normal nucleobase in nucleic acids. ... In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). ... The interaction of mRNA in a eukaryote cell. ... Look up translate in Wiktionary, the free dictionary. ...


DNA methylation in plants

Significant progress has been made in understanding DNA methylation in plants, specifically in the model plant, Arabidopsis thaliana. While in mammals, methylation mainly occurs on the cytosine in a CpG context, in plants the cytosine can be methylated in the CpG, CpNpG, and CpNpN context, where N represents any nucleotide but guinine.

The principal enzymes who’s function is to transfer and covalently attach methyl groups onto DNA (DNA methyltransferases) in A. thaliana are DRM2, MET1, and CMT3. All three share sequence homology on both the DNA and amino acid level. There are currently two classes of DNA methyltransferases: 1) the de-novo class, or enzymes that create new methylation marks on the DNA, and 2) a maintenance class that recognizes the methylation marks on the parental strand of DNA and transfers new methylation to the daughters strands after DNA replication. So far, DRM2 is the only enzyme that has been implicated as a de-novo DNA methyltransferase. DRM2 has also been shown, along with MET1 and CMT3 to be involved in maintaining methylation marks through DNA replication. [3] Other DNA methyltransferases are expressed in plants but have no known function (see [1]).

Binomial name Arabidopsis thaliana (L.) Heynh. ...


Currently, it is not clear how the cell determines the locations of de-novo DNA methylation, but evidence high suggest that for many, but not all location, RNA directed DNA methylation (RdDM) is involved. In RdDM, Specific RNA transcripts are produced from a genomic DNA template, and this RNA forms secondary structures called a double stranded RNA molecules. [4]The double stranded RNAs, through either the small interfering RNA (siRNA) or micro RNA (miRNA) pathways, direct de-novo DNA methylation of the original genomic location that produced the RNA.[4] This sort of mechanism is thought to be important in cellular defense against RNA viruses and/or transposons both of which often form a double stranded RNA that can mutagenic to the host genome. By methylating their genomic locations, through a still poorly understood mechanism, they are shut off and are no longer active in the cell protecting the genome from their mutagenic effect. Small interfering RNA (siRNA) are a class of 20-25 nucleotide-long RNA molecules that interfere with the expression of genes. ... In genetics, a miRNA (micro-RNA) is a form of single-stranded RNA which is typically 20-25 nucleotides long, and is thought to regulate the expression of other genes. ... An RNA virus is a virus that either uses RNA as its genetic material, or whose genetic material passes through an RNA intermediate during replication. ... Transposons are sequences of DNA that can move around to different positions within the genome of a single cell, a process called Transposition. ...


References

  1. ^ Dodge, Jonathan E.; Bernard H. Ramsahoyeb, Z. Galen Woa, Masaki Okanoa, En Li (May 2002). "De novo methylation of MMLV provirus in embryonic stem cells: CpG versus non-CpG methylation". Science Direct. 
  2. ^ Haines, Thomas R. (Dec 2001). "Allele-Specific Non-CpG Methylation of the Nf1 Gene during Early Mouse Development". Science Direct. 
  3. ^ Cao, Xiaofeng; Jacobsen, Steven E. (2003 Jul). "Locus-specific control of asymmetric and CpNpG methylation by the DRM and CMT3 methyltransferase genes". PNAS. 
  4. ^ Aufsatz, Werner; M. Florian Mette, Johannes van der Winden, Antonius J. M. Matzke, Marjori Matzke (2002 Dec). "RNA-directed DNA methylation in Arabidopsis". PNAS. 

Elseviers logo. ... Elseviers logo. ... The Proceedings of the National Academy of Sciences (USA), mostly commonly referred to as PNAS, is the official publication of the National Academy of Sciences of the United States of America. ... The Proceedings of the National Academy of Sciences (USA), mostly commonly referred to as PNAS, is the official publication of the National Academy of Sciences of the United States of America. ...

See also

Reprogramming refers to erasure and reestablishment of DNA methylation during mammalian development. ... In Biology, while the subject of genetics focuses on how organisms can inherit traits by inheriting genes from their parent(s), which encode information for cell function as sequences of DNA, epigenetics is sometimes used to refer to additional methods of biological inheritance that do not directly relate to the... Figure 1: Outline of bisulfite conversion of sample sequence of genomic DNA. Nucleotides in blue are unmethylated cytosines converted to uracils by bisulfite, while red nucleotides are 5-methylcytosines resistant to conversion. ...

External links


  Results from FactBites:
 
DNA methylation - Wikipedia, the free encyclopedia (711 words)
DNA methylation involves the addition of a methyl group to DNA — for example, to the number 5 carbon of the cytosine pyrimidine ring.
In adult somatic tissues, DNA methylation typically occurs in a CpG dinucleotide context; non-CpG methylation is prevalent in embryonic stem cells.
DNMT1 is the proposed maintenance methyltransferase that is responsible for copying DNA methylation patterns to the daughter strands during DNA replication.
  More results at FactBites »

 
 

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