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77-405: Razin may refer to: People [ edit ] Aharon Razin (1935–2019), Israeli biochemist Albert Razin (1940–2019), Udmurt language rights activist and Neopaganist who committed self-immolation Stenka Razin (Stepan Timofeyevich Razin, 1630–1671), Cossack leader Stenka Razin (film) , a short silent film Stenka Razin (Glazunov) ,

154-667: A CpG island in their promoter region. The majority of CpG islands are constitutively unmethylated and enriched for permissive chromatin modification such as H3K4 methylation. In somatic tissues, only 10% of CpG islands are methylated, the majority of them being located in intergenic and intragenic regions. DNA methylation was probably present at some extent in very early eukaryote ancestors. In virtually every organism analyzed, methylation in promoter regions correlates negatively with gene expression. CpG-dense promoters of actively transcribed genes are never methylated, but, reciprocally, transcriptionally silent genes do not necessarily carry

231-627: A DNA methylase-deficient genetic background makes Neurospora an important system in which to study DNA methylation. DNA methylation is largely absent from Dictyostelium discoideum where it appears to occur at about 0.006% of cytosines. In contrast, DNA methylation is widely distributed in Physarum polycephalum where 5-methylcytosine makes up as much as 8% of total cytosine Adenine or cytosine methylation are mediated by restriction modification systems of many bacteria , in which specific DNA sequences are methylated periodically throughout

308-577: A change in methylation status in atherosclerosis is the monocarboxylate transporter (MCT3), which produces a protein responsible for the transport of lactate and other ketone bodies out of many cell types, including vascular smooth muscle cells. In atherosclerosis patients, there is an increase in methylation of the CpG islands in exon 2, which decreases MCT3 protein expression. The downregulation of MCT3 impairs lactate transport and significantly increases smooth muscle cell proliferation, which further contributes to

385-608: A large proportion of carcinogenic gene silencing is a result of altered DNA methylation (see DNA methylation in cancer ). DNA methylation causing silencing in cancer typically occurs at multiple CpG sites in the CpG islands that are present in the promoters of protein coding genes. Altered expressions of microRNAs also silence or activate many genes in progression to cancer (see microRNAs in cancer ). Altered microRNA expression occurs through hyper/hypo-methylation of CpG sites in CpG islands in promoters controlling transcription of

462-467: A limited number of genes, how precisely DNA methylation absence causes the death of differentiated cells remain an open question. Due to the phenomenon of genomic imprinting , maternal and paternal genomes are differentially marked and must be properly reprogrammed every time they pass through the germline. Therefore, during gametogenesis , primordial germ cells must have their original biparental DNA methylation patterns erased and re-established based on

539-518: A methylated promoter. In mouse and human, around 60–70% of genes have a CpG island in their promoter region and most of these CpG islands remain unmethylated independently of the transcriptional activity of the gene, in both differentiated and undifferentiated cell types. Of note, whereas DNA methylation of CpG islands is unambiguously linked with transcriptional repression, the function of DNA methylation in CG-poor promoters remains unclear; albeit there

616-408: A possible increase in global genomic DNA methylation of white blood cells with more physical activity in non-Hispanics. A study that investigated the methylome of B cells along their differentiation cycle, using whole-genome bisulfite sequencing (WGBS), showed that there is a hypomethylation from the earliest stages to the most differentiated stages. The largest methylation difference is between

693-475: A potential link between DNA methylation and the progression of certain developmental processes. Global hypomethylation has also been implicated in the development and progression of cancer through different mechanisms. Typically, there is hypermethylation of tumor suppressor genes and hypomethylation of oncogenes . Generally, in progression to cancer, hundreds of genes are silenced or activated . Although silencing of some genes in cancers occurs by mutation,

770-608: A sort of primitive immune system, allowing the bacteria to protect themselves from infection by bacteriophage . E. coli DNA adenine methyltransferase (Dam) is an enzyme of ~32 kDa that does not belong to a restriction/modification system. The target recognition sequence for E. coli Dam is GATC, as the methylation occurs at the N6 position of the adenine in this sequence (G meATC). The three base pairs flanking each side of this site also influence DNA–Dam binding. Dam plays several key roles in bacterial processes, including mismatch repair,

847-449: A symphonic poem The Execution of Stepan Razin , a cantata by Shostakovich Places [ edit ] Razin, Ahar , East Azerbaijan Province, Iran Razin, Khoda Afarin , East Azerbaijan Province, Iran Razin, Hamadan , Hamadan Province, Iran Razin, Kermanshah , Kermanshah Province, Iran Razin, Markazi , Markazi Province, Iran See also [ edit ] Andrey Razin (disambiguation) Topics referred to by

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924-509: Is a global loss of DNA methylation during aging. In a study that analyzed the complete DNA methylomes of CD4 T cells in a newborn, a 26 years old individual and a 103 years old individual were observed that the loss of methylation is proportional to age. Hypomethylated CpGs observed in the centenarian DNAs compared with the neonates covered all genomic compartments (promoters, intergenic , intronic and exonic regions). However, some genes become hypermethylated with age, including genes for

1001-424: 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. Mice and rats have a third functional de novo methyltransferase enzyme named DNMT3C, which evolved as a paralog of Dnmt3b by tandem duplication in the common ancestral of Muroidea rodents. DNMT3C catalyzes

1078-431: Is almost exclusively found in CpG dinucleotides, with the cytosines on both strands being usually methylated. Non-CpG methylation can however be observed in embryonic stem cells , and has also been indicated in neural development . Furthermore, non-CpG methylation has also been observed in hematopoietic progenitor cells, and it occurred mainly in a CpApC sequence context. The DNA methylation landscape of vertebrates

1155-441: Is altered, and may influence how the individual's heart failure should be treated. In humans and other mammals, DNA methylation levels can be used to accurately estimate the age of tissues and cell types, forming an accurate epigenetic clock . A longitudinal study of twin children showed that, between the ages of 5 and 10, there was divergence of methylation patterns due to environmental rather than genetic influences. There

1232-403: Is currently unclear whether targeting DNMT1 alone is sufficient to reactivate tumor suppressor genes silenced by DNA methylation. Significant progress has been made in understanding DNA methylation in the model plant Arabidopsis thaliana . DNA methylation in plants differs from that of mammals: while DNA methylation in mammals mainly occurs on the cytosine nucleotide in a CpG site , in plants

1309-800: Is different from Wikidata All article disambiguation pages All disambiguation pages Aharon Razin Aharon Razin was raised in Petah Tikva . He began his academic studies at the Hebrew University of Jerusalem, majoring in physics and mathematics. He completed his M.A. and PhD in biochemistry, and did post-doctoral work at the California Institute of Technology. When he returned to Israel in 1971, he served as senior lecturer, associate professor and full professor of cellular biochemistry and human genetics at

1386-454: Is essential for normal development and is associated with a number of key processes including genomic imprinting , X-chromosome inactivation , repression of transposable elements , aging , and carcinogenesis . As of 2016, two nucleobases have been found on which natural, enzymatic DNA methylation takes place: adenine and cytosine . The modified bases are N -methyladenine, 5-methylcytosine and N -methylcytosine. Cytosine methylation

1463-492: Is evidenced by the under-representation of CpG dinucleotides in the human genome (they occur at only 21% of the expected frequency). (On the other hand, spontaneous deamination of unmethylated C residues gives rise to U residues, a change that is quickly recognized and repaired by the cell.) In mammals, the only exception for this global CpG depletion resides in a specific category of GC- and CpG-rich sequences termed CpG islands that are generally unmethylated and therefore retained

1540-467: Is highly enriched in the body of highly transcribed genes. In yeast at least, H3K36me3 recruits enzymes such as histone deacetylases to condense chromatin and prevent the activation of cryptic start sites. In mammals, DNMT3a and DNMT3b PWWP domain binds to H3K36me3 and the two enzymes are recruited to the body of actively transcribed genes. DNA methylation patterns are largely erased and then re-established between generations in mammals. Almost all of

1617-446: Is independent of DNMT2 activity." Further, highly sensitive mass spectrometry approaches, have now demonstrated the presence of low (0.07%) but significant levels of adenine methylation during the earliest stages of Drosophila embryogenesis. Many fungi have low levels (0.1 to 0.5%) of cytosine methylation, whereas other fungi have as much as 5% of the genome methylated. This value seems to vary both among species and among isolates of

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1694-513: Is linked to chromosomal instability and loss of imprinting, whereas hypermethylation is associated with promoters and can arise secondary to gene (oncogene suppressor) silencing, but might be a target for epigenetic therapy . In developmental contexts, dynamic changes in DNA methylation patterns also have significant implications. For instance, in rat limb buds, shifts in methylation status were associated with different stages of chondrogenesis, suggesting

1771-427: Is little evidence that it could be functionally relevant. DNA methylation may affect the transcription of genes in two ways. First, the methylation of DNA itself may physically impede the binding of transcriptional proteins to the gene, and 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

1848-492: Is not clear how the cell determines the locations of de novo DNA methylation, but evidence suggests that for many (though not all) locations, 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 double-stranded RNA molecules. The double-stranded RNAs, through either the small interfering RNA ( siRNA ) or microRNA ( miRNA ) pathways direct de-novo DNA methylation of

1925-432: Is present, DNA methylation is especially enriched in the body of highly transcribed genes. The function of gene body methylation is not well understood. A body of evidence suggests that it could regulate splicing and suppress the activity of intragenic transcriptional units (cryptic promoters or transposable elements). Gene-body methylation appears closely tied to H3K36 methylation. In yeast and mammals, H3K36 methylation

2002-429: Is rapid and is extremely robust in creating memories. In mice and in rats contextual fear conditioning, within 1–24 hours, it is associated with altered methylations of several thousand DNA cytosines in genes of hippocampus neurons. Twenty four hours after contextual fear conditioning, 9.2% of the genes in rat hippocampus neurons are differentially methylated. In mice, when examined at four weeks after conditioning,

2079-585: Is regulated by the methylation of GATC sites in the promoter region of the gene operon. The cells' environmental conditions just after DNA replication determine whether Dam is blocked from methylating a region proximal to or distal from the promoter region. Once the pattern of methylation has been created, the pilus gene transcription is locked in the on or off position until the DNA is again replicated. In E. coli , these pili operons have important roles in virulence in urinary tract infections. It has been proposed that inhibitors of Dam may function as antibiotics. On

2156-402: Is the marker that allows the repair apparatus of the cell to differentiate between the template and nascent strands. It has been shown that altering Dam activity in bacteria results in an increased spontaneous mutation rate. Bacterial viability is compromised in dam mutants that also lack certain other DNA repair enzymes, providing further evidence for the role of Dam in DNA repair. One region of

2233-462: Is the proposed maintenance methyltransferase that is responsible for copying DNA methylation patterns to the daughter strands during DNA replication. Mouse models with both copies of DNMT1 deleted are embryonic lethal at approximately day 9, due to the requirement of DNMT1 activity for development in mammalian cells. It is thought that DNMT3a and DNMT3b are the de novo methyltransferases that set up DNA methylation patterns early in development. DNMT3L

2310-522: Is thought nonetheless to represent a "locked" state that definitely inactivates transcription. In particular, DNA methylation appears critical for the maintenance of mono-allelic silencing in the context of genomic imprinting and X chromosome inactivation . In these cases, expressed and silent alleles differ by their methylation status, and loss of DNA methylation results in loss of imprinting and re-expression of Xist in somatic cells. During embryonic development, few genes change their methylation status, at

2387-428: Is very particular compared to other organisms. In mammals, around 75% of CpG dinucleotides are methylated in somatic cells , and DNA methylation appears as a default state that has to be specifically excluded from defined locations. By contrast, the genome of most plants, invertebrates, fungi, or protists show "mosaic" methylation patterns, where only specific genomic elements are targeted, and they are characterized by

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2464-1012: Is widespread in both eukaryotes and prokaryotes , even though the rate of cytosine DNA methylation can differ greatly between species: 14% of cytosines are methylated in Arabidopsis thaliana , 4% to 8% in Physarum , 7.6% in Mus musculus , 2.3% in Escherichia coli , 0.03% in Drosophila ; methylation is essentially undetectable in Dictyostelium ; and virtually absent (0.0002 to 0.0003%) from Caenorhabditis or fungi such as Saccharomyces cerevisiae and S. pombe (but not N. crassa ). Adenine methylation has been observed in bacterial, plant, and recently in mammalian DNA, but has received considerably less attention. Methylation of cytosine to form 5-methylcytosine occurs at

2541-692: The Chromatin Database ). Genome-wide levels of DNA methylation vary widely between plant species, and Arabidopsis cytosines tend to be less densely methylated than those in other plants. For example, ~92.5% of CpG cytosines are methylated in Beta vulgaris . The patterns of methylation also differ between cytosine sequence contexts; universally, CpG methylation is higher than CHG and CHH methylation, and CpG methylation can be found in both active genes and transposable elements, while CHG and CHH are usually relegated to silenced transposable elements. It

2618-550: The Louisa Gross Horwitz Prize together with Howard Cedar and Gary Felsenfeld . DNA methylation DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter , DNA methylation typically acts to repress gene transcription . In mammals, DNA methylation

2695-541: The de novo class or enzymes that create new methylation marks on the DNA; 2) a maintenance class that recognizes the methylation marks on the parental strand of DNA and transfers new methylation to the daughter strands after DNA replication. 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. Other DNA methyltransferases are expressed in plants but have no known function (see

2772-520: The estrogen receptor , p16 , insulin-like growth factor 2 , ELOVL2 and FHL2 High intensity exercise has been shown to result in reduced DNA methylation in skeletal muscle. Promoter methylation of PGC-1α and PDK4 were immediately reduced after high intensity exercise, whereas PPAR-γ methylation was not reduced until three hours after exercise. At the same time, six months of exercise in previously sedentary middle-age men resulted in increased methylation in adipose tissue . One study showed

2849-630: The hippocampus during memory establishment were summarized in 2022. That review also indicated the mechanisms by which the new patterns of methylation gave rise to new patterns of messenger RNA expression. These new messenger RNAs were then transported by messenger RNP particles (neuronal granules) to synapses of the neurons, where they could be translated into proteins. Active changes in neuronal DNA methylation and demethylation appear to act as controllers of synaptic scaling and glutamate receptor trafficking in learning and memory formation. In mammalian cells, DNA methylation occurs mainly at

2926-741: The microRNAs . Silencing of DNA repair genes through methylation of CpG islands in their promoters appears to be especially important in progression to cancer (see methylation of DNA repair genes in cancer ). Epigenetic modifications such as DNA methylation have been implicated in cardiovascular disease, including atherosclerosis . In animal models of atherosclerosis, vascular tissue, as well as blood cells such as mononuclear blood cells, exhibit global hypomethylation with gene-specific areas of hypermethylation. DNA methylation polymorphisms may be used as an early biomarker of atherosclerosis since they are present before lesions are observed, which may provide an early tool for detection and risk prevention. Two of

3003-513: The C5 position of CpG dinucleotides and is carried out by two general classes of enzymatic activities – maintenance methylation and de novo methylation. Maintenance methylation activity is necessary to preserve DNA methylation after every cellular DNA replication cycle. Without the DNA methyltransferase (DNMT), the replication machinery itself would produce daughter strands that are unmethylated and, over time, would lead to passive demethylation. DNMT1

3080-502: The DNA that keeps its hemimethylated status for longer is the origin of replication , which has an abundance of GATC sites. This is central to the bacterial mechanism for timing DNA replication. SeqA binds to the origin of replication, sequestering it and thus preventing methylation. Because hemimethylated origins of replication are inactive, this mechanism limits DNA replication to once per cell cycle. Expression of certain genes, for example, those coding for pilus expression in E. coli ,

3157-756: The Hebrew University Faculty of Medicine. In 1980, Razin was appointed head of the Department of Cellular Biochemistry at the Faculty of Medicine and Head of the Institute of Biochemistry. From 1988, he has held the Dr. Jacob Greenbaum Chair of Medical Sciences at Hebrew University. He is a member of the board of the Authority for Research and Development at the Hebrew University, chairman of

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3234-665: The Planning and Development Committee of the Faculty of Medicine and member of the Israel National Academy of Sciences advisory committee on the Human Genome. He now serves as professor emeritus in the Department for Developmental Biology & Cancer Research, The Institute For Medical Research, Israel-Canada (IMRIC). In his early studies, Razin examined the metabolism of nucleic acids and the biochemical faults in patients with gout and favism. He later studied

3311-459: The alternation of methylated and unmethylated domains. High CpG methylation in mammalian genomes has an evolutionary cost because it increases the frequency of spontaneous mutations. Loss of amino-groups occurs with a high frequency for cytosines, with different consequences depending on their methylation. Methylated C residues spontaneously deaminate to form T residues over time; hence CpG dinucleotides steadily deaminate to TpG dinucleotides, which

3388-469: The anticodon loop of aspartic acid transfer RNA. 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

3465-503: The atherosclerotic lesion. An ex vivo experiment using the demethylating agent Decitabine (5-aza-2 -deoxycytidine) was shown to induce MCT3 expression in a dose dependent manner, as all hypermethylated sites in the exon 2 CpG island became demethylated after treatment. This may serve as a novel therapeutic agent to treat atherosclerosis, although no human studies have been conducted thus far. In addition to atherosclerosis described above, specific epigenetic changes have been identified in

3542-698: The cell types targeted for DNA methylation polymorphisms are monocytes and lymphocytes, which experience an overall hypomethylation. One proposed mechanism behind this global hypomethylation is elevated homocysteine levels causing hyperhomocysteinemia , a known risk factor for cardiovascular disease. High plasma levels of homocysteine inhibit DNA methyltransferases, which causes hypomethylation. Hypomethylation of DNA affects genes that alter smooth muscle cell proliferation, cause endothelial cell dysfunction, and increase inflammatory mediators, all of which are critical in forming atherosclerotic lesions. High levels of homocysteine also result in hypermethylation of CpG islands in

3619-432: The cytosine can be methylated at CpG, CpHpG, and CpHpH sites, where H represents any nucleotide but not guanine. Overall, Arabidopsis DNA is highly methylated, mass spectrometry analysis estimated 14% of cytosines to be modified. Later, bisulfite sequencing data estimated that around 25% of Arabidopsis CG sites are methylated, but these levels vary based on the geographic location of Arabidopsis accessions (plants in

3696-413: The dynamic nature of DNA methylation in development. In this context, variations in global DNA methylation were observed across different developmental stages and culture conditions, highlighting the intricate regulation of methylation during organogenesis and its potential implications for regenerative medicine strategies. Whereas DNA methylation is not necessary per se for transcriptional silencing, it

3773-461: The enzymes' degradation. However, for decitabine to be active, it must be incorporated into the genome of the cell, which can cause mutations in the daughter cells if the cell does not die. In addition, 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

3850-404: The evolutionary driver for genome expansion remains unknown. There is a clear correlation between the size of the genome and CpG, suggesting that the DNA methylation of transposable elements led to a noticeable increase in the mass of DNA. A function that appears even more conserved than transposon silencing is positively correlated with gene expression. In almost all species where DNA methylation

3927-602: The expected CpG content. CpG islands are usually defined as regions with: 1) a length greater than 200bp, 2) a G+C content greater than 50%, 3) a ratio of observed to expected CpG greater than 0.6, although other definitions are sometimes used. Excluding repeated sequences, there are around 25,000 CpG islands in the human genome, 75% of which being less than 850bp long. They are major regulatory units and around 50% of CpG islands are located in gene promoter regions, while another 25% lie in gene bodies, often serving as alternative promoters. Reciprocally, around 60-70% of human genes have

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4004-588: The failing human heart. This may vary by disease etiology. For example, in ischemic heart failure DNA methylation changes have been linked to changes in gene expression that may direct gene expression associated with the changes in heart metabolism known to occur. Additional forms of heart failure (e.g. diabetic cardiomyopathy) and co-morbidities (e.g. obesity) must be explored to see how common these mechanisms are. Most strikingly, in failing human heart these changes in DNA methylation are associated with racial and socioeconomic status which further impact how gene expression

4081-437: The fine-tuning of gene regulation, its stability is perfect to ensure the permanent silencing of transposable elements . Transposon control is one of the most ancient functions of DNA methylation that is shared by animals, plants and multiple protists. It is even suggested that DNA methylation evolved precisely for this purpose. DNA methylation of transposable elements has been known to be related to genome expansion. However,

4158-475: The gene body, and current opinions on the function of DNA methylation is gene regulation via alternative splicing DNA methylation levels in Drosophila melanogaster are nearly undetectable. Sensitive methods applied to Drosophila DNA Suggest levels in the range of 0.1–0.3% of total cytosine. A 2014 study of found that the low level of methylation in fruit fruit flies appeared "at specific short motifs and

4235-783: The genome from their mutagenic effect. Recently, it was described that methylation of the DNA is the main determinant of embryogenic cultures formation from explants in woody plants and is regarded the main mechanism that explains the poor response of mature explants to somatic embryogenesis in the plants (Isah 2016). Diverse orders of insects show varied patterns of DNA methylation, from almost undetectable levels in flies to low levels in butterflies and higher in true bugs and some cockroaches (up to 14% of all CG sites in Blattella asahinai ). Functional DNA methylation has been discovered in Honey Bees. DNA methylation marks are mainly on

4312-400: 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 and cleaved. Bacterial genomic DNA is not recognized by these restriction enzymes. The methylation of native DNA acts as

4389-525: The hippocampus methylations and demethylations had been reset to the original naive conditions. The hippocampus is needed to form memories, but memories are not stored there. For such mice, at four weeks after contextual fear conditioning, substantial differential CpG methylations and demethylations occurred in cortical neurons during memory maintenance, and there were 1,223 differentially methylated genes in their anterior cingulate cortex. Mechanisms guiding new DNA methylations and new DNA demethylations in

4466-427: The implantation stage of the embryo, with CpG islands protected from methylation. This results in global repression and allows housekeeping genes to be expressed in all cells. In the post-implantation stage, methylation patterns are stage- and tissue-specific, with changes that would define each individual cell type lasting stably over a long period. Studies on rat limb buds during embryogenesis have further illustrated

4543-486: The important exception of many genes specifically expressed in the germline. DNA methylation appears absolutely required in differentiated cells , as knockout of any of the three competent DNA methyltransferase results in embryonic or post-partum lethality. By contrast, DNA methylation is dispensable in undifferentiated cell types, such as the inner cell mass of the blastocyst, primordial germ cells or embryonic stem cells. Since DNA methylation appears to directly regulate only

4620-469: The locus, such as histone deacetylases and other chromatin remodeling proteins that can modify histones , thereby forming compact, inactive chromatin, termed heterochromatin . 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

4697-579: The methylation of promoters of transposable elements during early spermatogenesis, an activity shown to be essential for their epigenetic repression and male fertility. It is yet unclear if in other mammals that do not have DNMT3C (like humans) rely on DNMT3B or DNMT3A for de novo methylation of transposable elements in the germline. Finally, DNMT2 (TRDMT1) has been identified as a DNA methyltransferase homolog, containing all 10 sequence motifs common to all DNA methyltransferases; however, DNMT2 (TRDMT1) does not methylate DNA but instead methylates cytosine-38 in

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4774-417: The methylations from the parents are erased, first during gametogenesis , and again in early embryogenesis , with demethylation and remethylation occurring each time. Demethylation in early embryogenesis occurs in the preimplantation period in two stages – initially in the zygote , then during the first few embryonic replication cycles of morula and blastula . A wave of methylation then takes place during

4851-550: The model filamentous fungus Neurospora crassa has a well-characterized methylation system. Several genes control methylation in Neurospora and mutation of the DNA methyl transferase, dim-2 , eliminates all DNA methylation but does not affect growth or sexual reproduction. While the Neurospora genome has very little repeated DNA, half of the methylation occurs in repeated DNA including transposon relics and centromeric DNA. The ability to evaluate other important phenomena in

4928-559: The north are more highly methylated than southern accessions). The principal Arabidopsis DNA methyltransferase enzymes, which transfer and covalently attach methyl groups onto DNA, are DRM2, MET1, and CMT3. Both the DRM2 and MET1 proteins share significant homology to the mammalian methyltransferases DNMT3 and DNMT1, respectively, whereas the CMT3 protein is unique to the plant kingdom. There are currently two classes of DNA methyltransferases: 1)

5005-583: The original C:G pair into a T:A pair, effectively changing a base and introducing a mutation. This misincorporated base will not be corrected during DNA replication as thymine is a DNA base. If the mismatch is not repaired and the cell enters the cell cycle the strand carrying the T will be complemented by an A in one of the daughter cells, such that the mutation becomes permanent. The near-universal use of thymine exclusively in DNA and uracil exclusively in RNA may have evolved as an error-control mechanism, to facilitate

5082-410: The original genomic location that produced the RNA. 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 be mutagenic to the host genome. By methylating their genomic locations, through an as yet poorly understood mechanism, they are shut off and are no longer active in the cell, protecting

5159-488: The promoter region of the estrogen receptor alpha (ERα) gene, causing its down regulation. ERα protects against atherosclerosis due to its action as a growth suppressor, causing the smooth muscle cells to remain in a quiescent state. Hypermethylation of the ERα promoter thus allows intimal smooth muscle cells to proliferate excessively and contribute to the development of the atherosclerotic lesion. Another gene that experiences

5236-474: The removal of uracils generated by the spontaneous deamination of cytosine. DNA methylation as well as many of its contemporary DNA methyltransferases have been thought to evolve from early world primitive RNA methylation activity and is supported by several lines of evidence. In plants and other organisms, DNA methylation is found in three different sequence contexts: CG (or CpG ), CHG or CHH (where H correspond to A, T or C). In mammals however, DNA methylation

5313-665: The role of DNA methylation in the control of gene expression." Razin's work on chemical changes in the DNA molecule focuses on the molecular process that turns on and off some 40,000 genes in the human body. In 2009, Razin won The EMET Prize for Art, Science and Culture . In 2011 he received the Canada Gairdner Award from the Gairdner Foundation , together with Howard Cedar and Adrian Peter Bird , for their "pioneering discoveries on DNA methylation and its role in gene expression." In 2016 he received

5390-426: The same 5 position on the pyrimidine ring where the DNA base thymine 's methyl group is located; the same position distinguishes thymine from the analogous RNA base uracil , which has no methyl group. Spontaneous deamination of 5-methylcytosine converts it to thymine. This results in a T:G mismatch. Repair mechanisms then correct it back to the original C:G pair; alternatively, they may substitute A for G, turning

5467-586: The same species. There is also evidence that DNA methylation may be involved in state-specific control of gene expression in fungi. However, at a detection limit of 250 attomoles by using ultra-high sensitive mass spectrometry DNA methylation was not confirmed in single cellular yeast species such as Saccharomyces cerevisiae or Schizosaccharomyces pombe , indicating that yeasts do not possess this DNA modification. Although brewers' yeast ( Saccharomyces ), fission yeast ( Schizosaccharomyces ), and Aspergillus flavus have no detectable DNA methylation,

5544-498: The same term [REDACTED] This disambiguation page lists articles associated with the title Razin . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=Razin&oldid=1246503395 " Categories : Disambiguation pages Place name disambiguation pages Disambiguation pages with surname-holder lists Hidden categories: Short description

5621-711: The sex of the transmitting parent. After fertilization, the paternal and maternal genomes are once again demethylated and remethylated (except for differentially methylated regions associated with imprinted genes). This reprogramming is likely required for totipotency of the newly formed embryo and erasure of acquired epigenetic changes. In many disease processes, such as cancer , gene promoter CpG islands acquire abnormal hypermethylation, which results in transcriptional silencing that can be inherited by daughter cells following cell division. Alterations of DNA methylation have been recognized as an important component of cancer development. Hypomethylation, in general, arises earlier and

5698-584: The specific mutation with the aid of a chemically synthesized DNA-sequence, DNA methylation in gene activity and methylation pattern production of single genes in the development of the fetus. In 2004, Razin was awarded the Israel Prize for biochemistry. In 2008, he was awarded the Wolf Prize in Medicine , jointly with Howard Cedar , for "their fundamental contributions to our understanding of

5775-420: The stages of germinal center B cells and memory B cells. Furthermore, this study showed that there is a similarity between B cell tumors and long-lived B cells in their DNA methylation signatures. Two reviews summarize evidence that DNA methylation alterations in brain neurons are important in learning and memory. Contextual fear conditioning (a form of associative learning) in animals, such as mice and rats,

5852-405: The timing of DNA replication, and gene expression. As a result of DNA replication, the status of GATC sites in the E. coli genome changes from fully methylated to hemimethylated. This is because adenine introduced into the new DNA strand is unmethylated. Re-methylation occurs within two to four seconds, during which time replication errors in the new strand are repaired. Methylation, or its absence,

5929-399: The transcriptional silencing of hypermethylated genes in "cancer." DNA methylation is a powerful transcriptional repressor, at least in CpG dense contexts. Transcriptional repression of protein-coding genes appears essentially limited to very specific classes of genes that need to be silent permanently and in almost all tissues. While DNA methylation does not have the flexibility required for

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