Methylation

Last updated

Methylation, in the chemical sciences, is the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These terms are commonly used in chemistry, biochemistry, soil science, and biology.

Contents

In biological systems, methylation is catalyzed by enzymes; such methylation can be involved in modification of heavy metals, regulation of gene expression, regulation of protein function, and RNA processing. In vitro methylation of tissue samples is also a way to reduce some histological staining artifacts. The reverse of methylation is demethylation.

In biology

In biological systems, methylation is accomplished by enzymes. Methylation can modify heavy metals and can regulate gene expression, RNA processing, and protein function. It is a key process underlying epigenetics. Sources of methyl groups include S-methylmethionine, methyl folate, methyl B12. [1]

Methanogenesis

Methanogenesis, the process that generates methane from CO2, involves a series of methylation reactions. These reactions are caused by a set of enzymes harbored by a family of anaerobic microbes. [2]

Cycle for methanogenesis, showing intermediates Methanogenesis cycle.png
Cycle for methanogenesis, showing intermediates

In reverse methanogenesis, methane is the methylating agent. [3]

O-methyltransferases

A wide variety of phenols undergo O-methylation to give anisole derivatives. This process, catalyzed by such enzymes as caffeoyl-CoA O-methyltransferase, is a key reaction in the biosynthesis of lignols, percursors to lignin, a major structural component of plants.

Plants produce flavonoids and isoflavones with methylations on hydroxyl groups, i.e. methoxy bonds. This 5-O-methylation affects the flavonoid's water solubility. Examples are 5-O-methylgenistein, 5-O-methylmyricetin, and 5-O-methylquercetin (azaleatin).

Proteins

Along with ubiquitination and phosphorylation, methylation is a major biochemical process for modifying protein function. The most prevalent protein methylations affect arginine and lysine residue of specific histones. Otherwise histidine, glutamate, asparagine, cysteine are susceptible to methylation. Some of these products include S-methylcysteine, two isomers of N-methylhistidine, and two isomers of N-methylarginine. [4]

Methionine synthase

The methylation reaction catalyzed by methionine synthase VitaminB12 2.png
The methylation reaction catalyzed by methionine synthase

Methionine synthase regenerates methionine (Met) from homocysteine (Hcy). The overall reaction transforms 5-methyltetrahydrofolate (N5-MeTHF) into tetrahydrofolate (THF) while transferring a methyl group to Hcy to form Met. Methionine Syntheses can be cobalamin-dependent and cobalamin-independent: Plants have both, animals depend on the methylcobalamin-dependent form.

In methylcobalamin-dependent forms of the enzyme, the reaction proceeds by two steps in a ping-pong reaction. The enzyme is initially primed into a reactive state by the transfer of a methyl group from N5-MeTHF to Co(I) in enzyme-bound cobalamin (Cob), forming methyl-cobalamin(Me-Cob) that now contains Me-Co(III) and activating the enzyme. Then, a Hcy that has coordinated to an enzyme-bound zinc to form a reactive thiolate reacts with the Me-Cob. The activated methyl group is transferred from Me-Cob to the Hcy thiolate, which regenerates Co(I) in Cob, and Met is released from the enzyme. [5]

Heavy metals: arsenic, mercury, cadmium

Biomethylation is the pathway for converting some heavy elements into more mobile or more lethal derivatives that can enter the food chain. The biomethylation of arsenic compounds starts with the formation of methanearsonates. Thus, trivalent inorganic arsenic compounds are methylated to give methanearsonate. S-adenosylmethionine is the methyl donor. The methanearsonates are the precursors to dimethylarsonates, again by the cycle of reduction (to methylarsonous acid) followed by a second methylation. [6] Related pathways are found in the microbial methylation of mercury to methylmercury.

Epigenetic methylation

DNA/RNA methylation

DNA methylation is the conversion of the cytosine to 5-methylcytosine. The formation of Me-CpG is catalyzed by the enzyme DNA methyltransferase. In vertebrates, DNA methylation typically occurs at CpG sites (cytosine-phosphate-guanine sites—that is, sites where a cytosine is directly followed by a guanine in the DNA sequence). In mammals, DNA methylation is common in body cells, [7] and methylation of CpG sites seems to be the default. [8] [9] Human DNA has about 80–90% of CpG sites methylated, but there are certain areas, known as CpG islands, that are CG-rich (high cytosine and guanine content, made up of about 65% CG residues), wherein none is 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. Methylation contributing to epigenetic inheritance can occur through either DNA methylation or protein methylation. Improper methylations of human genes can lead to disease development, [10] [11] including cancer. [12] [13]

In honey bees, DNA methylation is associated with alternative splicing and gene regulation based on functional genomic research published in 2013. [14] In addition, DNA methylation is associated with expression changes in immune genes when honey bees were under lethal viral infection. [15] Several review papers have been published on the topics of DNA methylation in social insects. [16] [17]

RNA methylation occurs in different RNA species viz. tRNA, rRNA, mRNA, tmRNA, snRNA, snoRNA, miRNA, and viral RNA. Different catalytic strategies are employed for RNA methylation by a variety of RNA-methyltransferases. RNA methylation is thought to have existed before DNA methylation in the early forms of life evolving on earth. [18]

N6-methyladenosine (m6A) is the most common and abundant methylation modification in RNA molecules (mRNA) present in eukaryotes. 5-methylcytosine (5-mC) also commonly occurs in various RNA molecules. Recent data strongly suggest that m6A and 5-mC RNA methylation affects the regulation of various biological processes such as RNA stability and mRNA translation, [19] and that abnormal RNA methylation contributes to etiology of human diseases. [20]

In social insects such as honey bees, RNA methylation is studied as a possible epigenetic mechanism underlying aggression via reciprocal crosses. [21]

Protein methylation

Protein methylation typically takes place on arginine or lysine amino acid residues in the protein sequence. [22] Arginine can be methylated once (monomethylated arginine) or twice, with either both methyl groups on one terminal nitrogen (asymmetric dimethylarginine) or one on both nitrogens (symmetric dimethylarginine), by protein arginine 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 from S-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. [23] [24] Protein methylation is one type of post-translational modification.

Evolution

Methyl metabolism is very ancient and can be found in all organisms on earth, from bacteria to humans, indicating the importance of methyl metabolism for physiology. [25] Indeed, pharmacological inhibition of global methylation in species ranging from human, mouse, fish, fly, roundworm, plant, algae, and cyanobacteria causes the same effects on their biological rhythms, demonstrating conserved physiological roles of methylation during evolution. [26]

In chemistry

The term methylation in organic chemistry refers to the alkylation process used to describe the delivery of a CH3 group. [27]

Electrophilic methylation

Methylations are commonly performed using electrophilic methyl sources such as iodomethane, [28] dimethyl sulfate, [29] [30] dimethyl carbonate, [31] or tetramethylammonium chloride. [32] Less common but more powerful (and more dangerous) methylating reagents include methyl triflate, [33] diazomethane, [34] and methyl fluorosulfonate (magic methyl). These reagents all react via SN2 nucleophilic substitutions. 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.

Iodomethane rxn1.png

The Purdie methylation is a specific for the methylation at oxygen of carbohydrates using iodomethane and silver oxide. [35]

Purdie methylation.png

Eschweiler–Clarke methylation

The Eschweiler–Clarke reaction is a method for methylation of amines. [36] This method avoids the risk of quaternization, which occurs when amines are methylated with methyl halides.

The Eschweiler-Clarke reaction is used to methylate amines. Eschweiler-Clarke Reaction.svg
The Eschweiler–Clarke reaction is used to methylate amines.

Diazomethane and trimethylsilyldiazomethane

Diazomethane and the safer analogue trimethylsilyldiazomethane methylate carboxylic acids, phenols, and even alcohols:

The method offers the advantage that the side products are easily removed from the product mixture. [37]

Nucleophilic methylation

Methylation sometimes involve use of nucleophilic methyl reagents. Strongly nucleophilic methylating agents include methyllithium (CH3Li) [38] or Grignard reagents such as methylmagnesium bromide (CH3MgX). [39] For example, CH3Li will add methyl groups to the carbonyl (C=O) of ketones and aldehyde.:

MeLi on acetone.png

Milder methylating agents include tetramethyltin, dimethylzinc, and trimethylaluminium. [40]

See also

Biology topics

Organic chemistry topics

Related Research Articles

<span class="mw-page-title-main">Epigenetics</span> Study of DNA modifications that do not change its sequence

In biology, epigenetics is the study of heritable traits, or a stable change of cell function, that happen without changes to the DNA sequence. The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic mechanism of inheritance. Epigenetics usually involves a change that is not erased by cell division, and affects the regulation of gene expression. Such effects on cellular and physiological phenotypic traits may result from environmental factors, or be part of normal development. They can lead to cancer.

<span class="mw-page-title-main">5-Methylcytosine</span> Chemical compound which is a modified DNA base

5-Methylcytosine is a methylated form of the DNA base cytosine (C) that regulates gene transcription and takes several other biological roles. When cytosine is methylated, the DNA maintains the same sequence, but the expression of methylated genes can be altered. 5-Methylcytosine is incorporated in the nucleoside 5-methylcytidine.

<span class="mw-page-title-main">DNA methyltransferase</span> Class of enzymes

In biochemistry, the DNA methyltransferase family of enzymes catalyze the transfer of a methyl group to DNA. DNA methylation serves a wide variety of biological functions. All the known DNA methyltransferases use S-adenosyl methionine (SAM) as the methyl donor.

<span class="mw-page-title-main">Histone methyltransferase</span> Histone-modifying enzymes

Histone methyltransferases (HMT) are histone-modifying enzymes, that catalyze the transfer of one, two, or three methyl groups to lysine and arginine residues of histone proteins. The attachment of methyl groups occurs predominantly at specific lysine or arginine residues on histones H3 and H4. Two major types of histone methyltranferases exist, lysine-specific and arginine-specific. In both types of histone methyltransferases, S-Adenosyl methionine (SAM) serves as a cofactor and methyl donor group.
The genomic DNA of eukaryotes associates with histones to form chromatin. The level of chromatin compaction depends heavily on histone methylation and other post-translational modifications of histones. Histone methylation is a principal epigenetic modification of chromatin that determines gene expression, genomic stability, stem cell maturation, cell lineage development, genetic imprinting, DNA methylation, and cell mitosis.

In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the gene products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in evolutionary developmental biology.

<i>S</i>-Adenosyl methionine Chemical compound found in all domains of life with largely unexplored effects

S-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throughout the body, most SAM is produced and consumed in the liver. More than 40 methyl transfers from SAM are known, to various substrates such as nucleic acids, proteins, lipids and secondary metabolites. It is made from adenosine triphosphate (ATP) and methionine by methionine adenosyltransferase. SAM was first discovered by Giulio Cantoni in 1952.

In chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed acetate esters or simply acetates. Deacetylation is the opposite reaction, the removal of an acetyl group from a chemical compound.

<span class="mw-page-title-main">DNA methylation</span> Biological process

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 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.

<span class="mw-page-title-main">Methionine synthase</span> Mammalian protein found in Homo sapiens

Methionine synthase (MS, MeSe, MTR) is responsible for the regeneration of methionine from homocysteine. In humans it is encoded by the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase). Methionine synthase forms part of the S-adenosylmethionine (SAMe) biosynthesis and regeneration cycle, and is the enzyme responsible for linking the cycle to one-carbon metabolism via the folate cycle. There are two primary forms of this enzyme, the Vitamin B12 (cobalamin)-dependent (MetH) and independent (MetE) forms, although minimal core methionine synthases that do not fit cleanly into either category have also been described in some anaerobic bacteria. The two dominant forms of the enzymes appear to be evolutionary independent and rely on considerably different chemical mechanisms. Mammals and other higher eukaryotes express only the cobalamin-dependent form. In contrast, the distribution of the two forms in Archaeplastida (plants and algae) is more complex. Plants exclusively possess the cobalamin-independent form, while algae have either one of the two, depending on species. Many different microorganisms express both the cobalamin-dependent and cobalamin-independent forms.

Histone methylation is a process by which methyl groups are transferred to amino acids of histone proteins that make up nucleosomes, which the DNA double helix wraps around to form chromosomes. Methylation of histones can either increase or decrease transcription of genes, depending on which amino acids in the histones are methylated, and how many methyl groups are attached. Methylation events that weaken chemical attractions between histone tails and DNA increase transcription because they enable the DNA to uncoil from nucleosomes so that transcription factor proteins and RNA polymerase can access the DNA. This process is critical for the regulation of gene expression that allows different cells to express different genes.

<span class="mw-page-title-main">Methyltransferase</span> Group of methylating enzymes

Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which contain a Rossmann fold for binding S-Adenosyl methionine (SAM). Class II methyltransferases contain a SET domain, which are exemplified by SET domain histone methyltransferases, and class III methyltransferases, which are membrane associated. Methyltransferases can also be grouped as different types utilizing different substrates in methyl transfer reactions. These types include protein methyltransferases, DNA/RNA methyltransferases, natural product methyltransferases, and non-SAM dependent methyltransferases. SAM is the classical methyl donor for methyltransferases, however, examples of other methyl donors are seen in nature. The general mechanism for methyl transfer is a SN2-like nucleophilic attack where the methionine sulfur serves as the leaving group and the methyl group attached to it acts as the electrophile that transfers the methyl group to the enzyme substrate. SAM is converted to S-Adenosyl homocysteine (SAH) during this process. The breaking of the SAM-methyl bond and the formation of the substrate-methyl bond happen nearly simultaneously. These enzymatic reactions are found in many pathways and are implicated in genetic diseases, cancer, and metabolic diseases. Another type of methyl transfer is the radical S-Adenosyl methionine (SAM) which is the methylation of unactivated carbon atoms in primary metabolites, proteins, lipids, and RNA.

<span class="mw-page-title-main">PRMT1</span> Protein-coding gene in the species Homo sapiens

Protein arginine N-methyltransferase 1 is an enzyme that in humans is encoded by the PRMT1 gene. The HRMT1L2 gene encodes a protein arginine methyltransferase that functions as a histone methyltransferase specific for histone H4.

<span class="mw-page-title-main">MTRR (gene)</span> Protein-coding gene in the species Homo sapiens

Methionine synthase reductase, also known as MSR, is an enzyme that in humans is encoded by the MTRR gene.

<span class="mw-page-title-main">PRMT6</span> Protein-coding gene in the species Homo sapiens

Protein arginine N-methyltransferase 6 is an enzyme that in humans is encoded by the PRMT6 gene.

<span class="mw-page-title-main">Tudor domain</span>

In molecular biology, a Tudor domain is a conserved protein structural domain originally identified in the Tudor protein encoded in Drosophila. The Tudor gene was found in a Drosophila screen for maternal factors that regulate embryonic development or fertility. Mutations here are lethal for offspring, inspiring the name Tudor, as a reference to the Tudor King Henry VIII and the several miscarriages experienced by his wives.

<span class="mw-page-title-main">EHMT1</span> Protein-coding gene in the species Homo sapiens

Euchromatic histone-lysine N-methyltransferase 1, also known as G9a-like protein (GLP), is a protein that in humans is encoded by the EHMT1 gene.

Protein methylation is a type of post-translational modification featuring the addition of methyl groups to proteins. It can occur on the nitrogen-containing side-chains of arginine and lysine, but also at the amino- and carboxy-termini of a number of different proteins. In biology, methyltransferases catalyze the methylation process, activated primarily by S-adenosylmethionine. Protein methylation has been most studied in histones, where the transfer of methyl groups from S-adenosyl methionine is catalyzed by histone methyltransferases. Histones that are methylated on certain residues can act epigenetically to repress or activate gene expression.

<span class="mw-page-title-main">Epigenetics of human herpesvirus latency</span>

Human herpes viruses, also known as HHVs, are part of a family of DNA viruses that cause several diseases in humans. One of the most notable functions of this virus family is their ability to enter a latent phase and lay dormant within animals for extended periods of time. The mechanism that controls this is very complex because expression of viral proteins during latency is decreased a great deal, meaning that the virus must have transcription of its genes repressed. There are many factors and mechanisms that control this process and epigenetics is one way this is accomplished. Epigenetics refers to persistent changes in expression patterns that are not caused by changes to the DNA sequence. This happens through mechanisms such as methylation and acetylation of histones, DNA methylation, and non-coding RNAs (ncRNA). Altering the acetylation of histones creates changes in expression by changing the binding affinity of histones to DNA, making it harder or easier for transcription machinery to access the DNA. Methyl and acetyl groups can also act as binding sites for transcription factors and enzymes that further modify histones or alter the DNA itself.

Pharmacoepigenetics is an emerging field that studies the underlying epigenetic marking patterns that lead to variation in an individual's response to medical treatment.

Transgenerational epigenetic inheritance in plants involves mechanisms for the passing of epigenetic marks from parent to offspring that differ from those reported in animals. There are several kinds of epigenetic markers, but they all provide a mechanism to facilitate greater phenotypic plasticity by influencing the expression of genes without altering the DNA code. These modifications represent responses to environmental input and are reversible changes to gene expression patterns that can be passed down through generations. In plants, transgenerational epigenetic inheritance could potentially represent an evolutionary adaptation for sessile organisms to quickly adapt to their changing environment.

References

  1. ↑ Ragsdale, Stephen W. (2008). "Catalysis of Methyl Group Transfers Involving Tetrahydrofolate and B12". Folic Acid and Folates. Vitamins & Hormones. Vol. 79. pp. 293–324. doi:10.1016/S0083-6729(08)00410-X. ISBN   978-0-12-374232-2. PMC   3037834 . PMID   18804699.
  2. ↑ Thauer, R. K., "Biochemistry of Methanogenesis: a Tribute to Marjory Stephenson", Microbiology, 1998, volume 144, pages 2377-2406.
  3. ↑ Timmers, Peer H. A.; Welte, Cornelia U.; Koehorst, Jasper J.; Plugge, Caroline M.; Jetten, Mike S. M.; Stams, Alfons J. M. (2017). "Reverse Methanogenesis and Respiration in Methanotrophic Archaea". Archaea. 2017: 1–22. doi: 10.1155/2017/1654237 .
  4. ↑ Clarke, Steven G. (2018). "The ribosome: A hot spot for the identification of new types of protein methyltransferases". Journal of Biological Chemistry. 293 (27): 10438–10446. doi: 10.1074/jbc.AW118.003235 . PMC   6036201 . PMID   29743234.
  5. ↑ Matthews, R. G.; Smith, A. E.; Zhou, Z. S.; Taurog, R. E.; Bandarian, V.; Evans, J. C.; Ludwig, M. (2003). "Cobalamin-Dependent and Cobalamin-Independent Methionine Synthases: Are There Two Solutions to the Same Chemical Problem?". Helvetica Chimica Acta. 86 (12): 3939–3954. doi:10.1002/hlca.200390329.
  6. ↑ Styblo, M.; Del Razo, L. M.; Vega, L.; Germolec, D. R.; LeCluyse, E. L.; Hamilton, G. A.; Reed, W.; Wang, C.; Cullen, W. R.; Thomas, D. J. (2000). "Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells". Archives of Toxicology. 74 (6): 289–299. doi:10.1007/s002040000134. PMID   11005674. S2CID   1025140.
  7. ↑ Tost J (2010). "DNA methylation: an introduction to the biology and the disease-associated changes of a promising biomarker". Mol Biotechnol. 44 (1): 71–81. doi:10.1007/s12033-009-9216-2. PMID   19842073. S2CID   20307488.
  8. ↑ Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR (November 2009). "Human DNA methylomes at base resolution show widespread epigenomic differences". Nature. 462 (7271): 315–22. Bibcode:2009Natur.462..315L. doi:10.1038/nature08514. PMC   2857523 . PMID   19829295.
  9. ↑ Stadler MB, Murr R, Burger L, Ivanek R, Lienert F, Schöler A, van Nimwegen E, Wirbelauer C, Oakeley EJ, Gaidatzis D, Tiwari VK, Schübeler D (December 2011). "DNA-binding factors shape the mouse methylome at distal regulatory regions". Nature. 480 (7378): 490–5. doi: 10.1038/nature11086 . PMID   22170606.
  10. ↑ Rotondo JC, Selvatici R, Di Domenico M, Marci R, Vesce F, Tognon M, Martini F (September 2013). "Methylation loss at H19 imprinted gene correlates with methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples from infertile males". Epigenetics. 8 (9): 990–7. doi:10.4161/epi.25798. PMC   3883776 . PMID   23975186.
  11. ↑ Rotondo JC, Bosi S, Bazzan E, Di Domenico M, De Mattei M, Selvatici R, Patella A, Marci R, Tognon M, Martini F (December 2012). "Methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples of infertile couples correlates with recurrent spontaneous abortion". Human Reproduction. 27 (12): 3632–8. doi: 10.1093/humrep/des319 . hdl: 11392/1689715 . PMID   23010533.
  12. ↑ Rotondo JC, Borghi A, Selvatici R, Magri E, Bianchini E, Montinari E, Corazza M, Virgili A, Tognon M, Martini F (2016). "Hypermethylation-Induced Inactivation of the IRF6 Gene as a Possible Early Event in Progression of Vulvar Squamous Cell Carcinoma Associated With Lichen Sclerosus". JAMA Dermatology. 152 (8): 928–33. doi:10.1001/jamadermatol.2016.1336. PMID   27223861.
  13. ↑ Rotondo JC, Borghi A, Selvatici R, Mazzoni E, Bononi I, Corazza M, Kussini J, Montinari E, Gafà R, Tognon M, Martini F (2018). "Association of Retinoic Acid Receptor β Gene With Onset and Progression of Lichen Sclerosus-Associated Vulvar Squamous Cell Carcinoma". JAMA Dermatology. 154 (7): 819–823. doi:10.1001/jamadermatol.2018.1373. PMC   6128494 . PMID   29898214.
  14. ↑ Li-Byarlay, Hongmei; Li, Yang; Stroud, Hume; Feng, Suhua; Newman, Thomas C.; Kaneda, Megan; Hou, Kirk K.; Worley, Kim C.; Elsik, Christine G.; Wickline, Samuel A.; Jacobsen, Steven E.; Ma, Jian; Robinson, Gene E. (30 July 2013). "RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee". Proceedings of the National Academy of Sciences. 110 (31): 12750–12755. Bibcode:2013PNAS..11012750L. doi: 10.1073/pnas.1310735110 . PMC   3732956 . PMID   23852726.
  15. ↑ Li-Byarlay, Hongmei; Boncristiani, Humberto; Howell, Gary; Herman, Jake; Clark, Lindsay; Strand, Micheline K.; Tarpy, David; Rueppell, Olav (24 September 2020). "Transcriptomic and Epigenomic Dynamics of Honey Bees in Response to Lethal Viral Infection". Frontiers in Genetics. 11. doi: 10.3389/fgene.2020.566320 . PMC   7546774 . PMID   33101388.
  16. ↑ Li-Byarlay, Hongmei (19 May 2016). "The Function of DNA Methylation Marks in Social Insects". Frontiers in Ecology and Evolution. 4. doi: 10.3389/fevo.2016.00057 .
  17. ↑ Wang, Ying; Li-Byarlay, Hongmei (2015). Physiological and Molecular Mechanisms of Nutrition in Honey Bees. Advances in Insect Physiology. Vol. 49. pp. 25–58. doi:10.1016/bs.aiip.2015.06.002. ISBN   978-0-12-802586-4.
  18. ↑ Rana, Ajay K.; Ankri, Serge (6 June 2016). "Reviving the RNA World: An Insight into the Appearance of RNA Methyltransferases". Frontiers in Genetics. 7: 99. doi: 10.3389/fgene.2016.00099 . PMC   4893491 . PMID   27375676.
  19. ↑ Choi, Junhong; Ieong, Ka-Weng; Demirci, Hasan; Chen, Jin; Petrov, Alexey; Prabhakar, Arjun; O'Leary, Seán E; Dominissini, Dan; Rechavi, Gideon; Soltis, S Michael; Ehrenberg, Måns; Puglisi, Joseph D (February 2016). "N6-methyladenosine in mRNA disrupts tRNA selection and translation-elongation dynamics". Nature Structural & Molecular Biology. 23 (2): 110–115. doi:10.1038/nsmb.3148. PMC   4826618 . PMID   26751643.
  20. ↑ Stewart, Kendal (15 September 2017). "Methylation (MTHFR) Testing & Folate Deficiency". Archived from the original on 12 October 2017. Retrieved 11 October 2017.
  21. ↑ Bresnahan, Sean T.; Lee, Ellen; Clark, Lindsay; Ma, Rong; Rangel, Juliana; Grozinger, Christina M.; Li-Byarlay, Hongmei (12 June 2023). "Examining parent-of-origin effects on transcription and RNA methylation in mediating aggressive behavior in honey bees (Apis mellifera)". BMC Genomics. 24 (1): 315. doi: 10.1186/s12864-023-09411-4 . PMC   10258952 . PMID   37308882.
  22. ↑ Walsh, Christopher (2006). "Protein Methylation". Posttranslational Modification of Proteins: Expanding Nature's Inventory. Roberts and Company Publishers. pp. 121–149. ISBN   978-0-9747077-3-0.
  23. ↑ Grewal, Shiv IS; Rice, Judd C (June 2004). "Regulation of heterochromatin by histone methylation and small RNAs". Current Opinion in Cell Biology. 16 (3): 230–238. doi:10.1016/j.ceb.2004.04.002. PMID   15145346.
  24. ↑ Nakayama, Jun-ichi; Rice, Judd C.; Strahl, Brian D.; Allis, C. David; Grewal, Shiv I. S. (6 April 2001). "Role of Histone H3 Lysine 9 Methylation in Epigenetic Control of Heterochromatin Assembly". Science. 292 (5514): 110–113. Bibcode:2001Sci...292..110N. doi:10.1126/science.1060118. PMID   11283354.
  25. ↑ Kozbial, Piotr Z; Mushegian, Arcady R (December 2005). "Natural history of S-adenosylmethionine-binding proteins". BMC Structural Biology. 5 (1): 19. doi: 10.1186/1472-6807-5-19 . PMC   1282579 . PMID   16225687.
  26. ↑ Fustin, Jean-Michel; Ye, Shiqi; Rakers, Christin; Kaneko, Kensuke; Fukumoto, Kazuki; Yamano, Mayu; Versteven, Marijke; Grünewald, Ellen; Cargill, Samantha J.; Tamai, T. Katherine; Xu, Yao; Jabbur, Maria Luísa; Kojima, Rika; Lamberti, Melisa L.; Yoshioka-Kobayashi, Kumiko; Whitmore, David; Tammam, Stephanie; Howell, P. Lynne; Kageyama, Ryoichiro; Matsuo, Takuya; Stanewsky, Ralf; Golombek, Diego A.; Johnson, Carl Hirschie; Kakeya, Hideaki; van Ooijen, Gerben; Okamura, Hitoshi (6 May 2020). "Methylation deficiency disrupts biological rhythms from bacteria to humans". Communications Biology. 3 (1): 211. doi: 10.1038/s42003-020-0942-0 . PMC   7203018 . PMID   32376902.
  27. ↑ "Aromatic Substitution, Nucleophilic and Organometallic". March's Advanced Organic Chemistry. 2006. pp. 853–933. doi:10.1002/9780470084960.ch13. ISBN   978-0-471-72091-1.
  28. ↑ Vyas, G. N.; Shah, N. M. (1951). "Quninacetophenone monomethyl ether". Organic Syntheses . 31: 90. doi:10.15227/orgsyn.031.0090.
  29. ↑ Hiers, G. S. (1929). "Anisole". Organic Syntheses. 9: 12. doi:10.15227/orgsyn.009.0012.
  30. ↑ Icke, Roland N.; Redemann, Ernst; Wisegarver, Burnett B.; Alles, Gordon A. (1949). "m-Methoxybenzaldehyde". Organic Syntheses. 29: 63. doi:10.15227/orgsyn.029.0063.
  31. ↑ Tundo, Pietro; Selva, Maurizio; Bomben, Andrea (1999). "Mono-C-methylathion of arylacetonitriles and methyl arylacetates by dimethyl carbonate: a general method for the synthesis of pure 2-arylpropionic acids. 2-Phenylpropionic acid". Organic Syntheses. 76: 169. doi:10.15227/orgsyn.076.0169.
  32. ↑ Nenad, Maraš; Polanc, Slovenko; Kočevar, Marijan (2008). "Microwave-assisted methylation of phenols with tetramethylammonium chloride in the presence of K2CO3 or Cs2CO3". Tetrahedron. 64 (51): 11618–11624. doi:10.1016/j.tet.2008.10.024.
  33. ↑ Poon, Kevin W. C.; Albiniak, Philip A.; Dudley, Gregory B. (2007). "Protection of alcohols using 2-benzyloxy-1-methylpyridinium trifluoromethanesulfanonate: Methyl (R)-(-)-3-benzyloxy-2-methyl propanoate". Organic Syntheses. 84: 295. doi:10.15227/orgsyn.084.0295.
  34. ↑ Neeman, M.; Johnson, William S. (1961). "Cholestanyl methyl ether". Organic Syntheses. 41: 9. doi:10.15227/orgsyn.041.0009.
  35. ↑ Purdie, T.; Irvine, J. C. (1903). "C.?The alkylation of sugars". Journal of the Chemical Society, Transactions. 83: 1021–1037. doi:10.1039/CT9038301021.
  36. ↑ Icke, Roland N.; Wisegarver, Burnett B.; Alles, Gordon A. (1945). "β-Phenylethyldimethylamine". Organic Syntheses. 25: 89. doi:10.15227/orgsyn.025.0089.
  37. ↑ Shioiri T, Aoyama T, Snowden T (2001). "Trimethylsilyldiazomethane". Encyclopedia of Reagents for Organic Synthesis. e-EROS Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rt298.pub2. ISBN   978-0-471-93623-7.
  38. ↑ Lipsky, Sharon D.; Hall, Stan S. (1976). "Aromatic Hydrocarbons from aromatic ketones and aldehydes: 1,1-Diphenylethane". Organic Syntheses. 55: 7. doi:10.15227/orgsyn.055.0007.
  39. ↑ Grummitt, Oliver; Becker, Ernest I. (1950). "trans-1-Phenyl-1,3-butadiene". Organic Syntheses. 30: 75. doi:10.15227/orgsyn.030.0075.
  40. ↑ Negishi, Ei-ichi; Matsushita, Hajime (1984). "Palladium-Catalyzed Synthesis of 1,4-Dienes by Allylation of Alkenyalane: α-Farnesene". Organic Syntheses. 62: 31. doi:10.15227/orgsyn.062.0031.
  41. ↑ Wienken CJ, Baaske P, Duhr S, Braun D (2011). "Thermophoretic melting curves quantify the conformation and stability of RNA and DNA". Nucleic Acids Research. 39 (8): e52. doi:10.1093/nar/gkr035. PMC   3082908 . PMID   21297115.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.