Editing Methylation (section)

====DNA methylation ====
[[DNA methylation]] is the conversion of the cytosine to [[5-methylcytosine]]. The formation of Me-CpG is [[Catalysis|catalyzed]] by the enzyme [[DNA methyltransferase]]. In vertebrates, DNA methylation typically occurs at [[CpG site]]s (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,<ref name="pmid19842073">{{cite journal| author=Tost J| title=DNA methylation: an introduction to the biology and the disease-associated changes of a promising biomarker. | journal=Mol Biotechnol | year= 2010 | volume= 44 | issue= 1 | pages= 71–81 | pmid=19842073 | doi=10.1007/s12033-009-9216-2 | s2cid=20307488 }}</ref> and methylation of CpG sites seems to be the default.<ref name="ReferenceC">{{cite journal | vauthors = 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 | title = Human DNA methylomes at base resolution show widespread epigenomic differences | journal = Nature | volume = 462 | issue = 7271 | pages = 315–22 | date = November 2009 | pmid = 19829295 | pmc = 2857523 | doi = 10.1038/nature08514 | bibcode = 2009Natur.462..315L }}</ref><ref>{{cite journal | vauthors = 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 | title = DNA-binding factors shape the mouse methylome at distal regulatory regions | journal = Nature | volume = 480 | issue = 7378 | pages = 490–5 | date = December 2011 | pmid = 22170606 | doi = 10.1038/nature11086 | doi-access = free }}</ref> Human DNA has about 80–90% of CpG sites methylated, but there are certain areas, known as [[CpG site#CpG islands|CpG islands]], that are CG-rich (high cytosine and guanine content, made up of about 65% CG [[Residue (chemistry)|residues]]), wherein none is methylated. These are associated with the [[Promoter (genetics)|promoters]] of 56% of mammalian genes, including all [[Housekeeping gene|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,<ref name = "Rotondo_2013">{{cite journal | vauthors = Rotondo JC, Selvatici R, Di Domenico M, Marci R, Vesce F, Tognon M, Martini F | title = Methylation loss at H19 imprinted gene correlates with methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples from infertile males | journal = Epigenetics | volume = 8 | issue = 9 | pages = 990–7 | date = September 2013 | pmid = 23975186 | pmc = 3883776 | doi = 10.4161/epi.25798 }}</ref><ref name = "Rotondo_2012">{{cite journal | vauthors = Rotondo JC, Bosi S, Bazzan E, Di Domenico M, De Mattei M, Selvatici R, Patella A, Marci R, Tognon M, Martini F | title = Methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples of infertile couples correlates with recurrent spontaneous abortion | journal = Human Reproduction | volume = 27 | issue = 12 | pages = 3632–8 | date = December 2012 | pmid = 23010533 | doi = 10.1093/humrep/des319 |url= https://academic.oup.com/humrep/article/27/12/3632/651064| doi-access = free | hdl = 11392/1689715 | hdl-access = free }}</ref> including cancer.<ref name="pmid27223861">{{cite journal |vauthors=Rotondo JC, Borghi A, Selvatici R, Magri E, Bianchini E, Montinari E, Corazza M, Virgili A, Tognon M, Martini F | title = Hypermethylation-Induced Inactivation of the IRF6 Gene as a Possible Early Event in Progression of Vulvar Squamous Cell Carcinoma Associated With Lichen Sclerosus | journal = JAMA Dermatology | volume = 152| issue = 8 | pages = 928–33 |date=2016 | pmid = 27223861 | doi = 10.1001/jamadermatol.2016.1336 }}</ref><ref name = "Rotondo_2018">{{cite journal | vauthors = Rotondo JC, Borghi A, Selvatici R, Mazzoni E, Bononi I, Corazza M, Kussini J, Montinari E, Gafà R, Tognon M, Martini F | title = Association of Retinoic Acid Receptor β Gene With Onset and Progression of Lichen Sclerosus-Associated Vulvar Squamous Cell Carcinoma | journal = JAMA Dermatology | volume = 154| issue = 7| pages = 819–823 | date = 2018 | pmid = 29898214| doi = 10.1001/jamadermatol.2018.1373| pmc = 6128494 }}</ref>

In [[Honey bee|honey bees]], DNA methylation is associated with alternative splicing and gene regulation based on functional genomic research published in 2013.<ref>{{cite journal |last1=Li-Byarlay |first1=Hongmei |last2=Li |first2=Yang |last3=Stroud |first3=Hume |last4=Feng |first4=Suhua |last5=Newman |first5=Thomas C. |last6=Kaneda |first6=Megan |last7=Hou |first7=Kirk K. |last8=Worley |first8=Kim C. |last9=Elsik |first9=Christine G. |last10=Wickline |first10=Samuel A. |last11=Jacobsen |first11=Steven E. |last12=Ma |first12=Jian |last13=Robinson |first13=Gene E. |title=RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee |journal=Proceedings of the National Academy of Sciences |date=30 July 2013 |volume=110 |issue=31 |pages=12750–12755 |doi=10.1073/pnas.1310735110 |doi-access=free |pmid=23852726 |pmc=3732956 |bibcode=2013PNAS..11012750L }}</ref> In addition, DNA methylation is associated with expression changes in immune genes when honey bees were under lethal viral infection.<ref>{{cite journal |last1=Li-Byarlay |first1=Hongmei |last2=Boncristiani |first2=Humberto |last3=Howell |first3=Gary |last4=Herman |first4=Jake |last5=Clark |first5=Lindsay |last6=Strand |first6=Micheline K. |last7=Tarpy |first7=David |last8=Rueppell |first8=Olav |title=Transcriptomic and Epigenomic Dynamics of Honey Bees in Response to Lethal Viral Infection |journal=Frontiers in Genetics |date=24 September 2020 |volume=11 |doi=10.3389/fgene.2020.566320 |doi-access=free |pmid=33101388 |pmc=7546774 }}</ref> Several review papers have been published on the topics of DNA methylation in social insects.<ref>{{cite journal |last1=Li-Byarlay |first1=Hongmei |title=The Function of DNA Methylation Marks in Social Insects |journal=Frontiers in Ecology and Evolution |date=19 May 2016 |volume=4 |doi=10.3389/fevo.2016.00057 |doi-access=free }}</ref><ref>{{cite book |doi=10.1016/bs.aiip.2015.06.002 |title=Physiological and Molecular Mechanisms of Nutrition in Honey Bees |series=Advances in Insect Physiology |date=2015 |last1=Wang |first1=Ying |last2=Li-Byarlay |first2=Hongmei |volume=49 |pages=25–58 |isbn=978-0-12-802586-4 }}</ref>