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{{Short description|Protein-coding gene in the species Homo sapiens}}
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{{PBB|geneid=10919}}
{{Use dmy dates|date=November 2018}}
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'''Histone-lysine N-methyltransferase, H3 lysine-9 specific 3''' is a [[histone methyltransferase]] that in humans is encoded by the ''EHMT2'' [[gene]].<ref name="pmid8457211">{{cite journal | author = Milner CM, Campbell RD | title = The G9a gene in the human major histocompatibility complex encodes a novel protein containing ankyrin-like repeats | journal = Biochem J | volume = 290 ( Pt 3) | issue = Pt 3| pages = 811–8 | year = 1993 | month = Apr | pmid = 8457211 | pmc = 1132354 | doi = }}</ref><ref name="pmid11316813">{{cite journal | author = Tachibana M, Sugimoto K, Fukushima T, Shinkai Y | title = Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3 | journal = J Biol Chem | volume = 276 | issue = 27 | pages = 25309–17 | year = 2001 | month = Jul | pmid = 11316813 | pmc = | doi = 10.1074/jbc.M101914200 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: EHMT2 euchromatic histone-lysine N-methyltransferase 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10919| accessdate = }}</ref>
{{Infobox_gene}}
{{technical|ate=July 2018|date=July 2018}}
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'''Euchromatic histone-lysine N-methyltransferase 2''' ('''EHMT2'''), also known as '''G9a''', is a [[histone methyltransferase]] [[enzyme]] that in humans is encoded by the ''EHMT2'' [[gene]].<ref name="pmid8457211">{{cite journal | vauthors = Milner CM, Campbell RD | title = The G9a gene in the human major histocompatibility complex encodes a novel protein containing ankyrin-like repeats | journal = The Biochemical Journal | volume = 290 | issue = Pt 3 | pages = 811–8 | date = March 1993 | pmid = 8457211 | pmc = 1132354 | doi = 10.1042/bj2900811 }}</ref><ref name="pmid11316813">{{cite journal | vauthors = Tachibana M, Sugimoto K, Fukushima T, Shinkai Y | title = Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3 | journal = The Journal of Biological Chemistry | volume = 276 | issue = 27 | pages = 25309–17 | date = July 2001 | pmid = 11316813 | doi = 10.1074/jbc.M101914200 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: EHMT2 euchromatic histone-lysine N-methyltransferase 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10919 }}</ref> G9a deposits the mono- and di-methylated states of [[histone H3]] at [[lysine]] residue 9 (i.e., [[H3K9me1]] and [[H3K9me2]]) and lysine residue 27 ([[H3K27me1]] and H3K27me2).<ref name="pmid26472529">{{cite book | vauthors = Nestler EJ | title = Role of the Brain's Reward Circuitry in Depression: Transcriptional Mechanisms | journal = International Review of Neurobiology | volume = 124 | pages = 151–70 | date = August 2015 | pmid = 26472529 | pmc = 4690450 | doi = 10.1016/bs.irn.2015.07.003 | isbn = 9780128015834 }}</ref><ref name="Histome G9a" /> The presence of H3K9me1/2 is usually associated with [[gene silencing]].


== Function ==
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
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| summary_text = A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. This gene is found near this cluster; it was mapped near the gene for C2 within a 120-kb region that included a HSP70 gene pair. These genes are all within the human major histocompatibility complex class III region. This gene was thought to be two different genes, NG36 and G9a, adjacent to each other but a recent publication shows that there is only a single gene. The protein encoded by this gene is thought to be involved in intracellular protein-protein interaction. There are three alternatively spliced transcript variants of this gene but only two are fully described.<ref name="entrez"/>
}}


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A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. This gene is found near this cluster; it was mapped near the gene for C2 within a 120-kb region that included a HSP70 gene pair. These genes are all within the human major histocompatibility complex class III region. This gene was thought to be two different genes, NG36 and G9a, adjacent to each other but a recent publication shows that there is only a single gene. The protein encoded by this gene is thought to be involved in intracellular protein-protein interaction. There are three alternatively spliced transcript variants of this gene but only two are fully described.<ref name="entrez"/>
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==Interactions==
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EHMT2 has been shown to [[Protein-protein interaction|interact]] with [[KIAA0515]].<ref name=pmid16189514>{{cite journal |last=Rual |first=Jean-François |authorlink= |coauthors=Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc |year=2005|month=Oct. |title=Towards a proteome-scale map of the human protein-protein interaction network |journal=[[Nature (journal)|Nature]] |volume=437 |issue=7062 |pages=1173–8 |publisher= |location = England| pmid = 16189514 |doi = 10.1038/nature04209 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref>


G9a and [[G9a-like protein]], another histone-lysine N-methyltransferase, catalyze the synthesis of [[H3K9me2]], which is a [[repressor|repressive]] mark.<ref name="pmid26472529" /><ref name="Histome G9a">{{cite web |title=Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 |url=http://www.actrec.gov.in/histome/enzyme_sp.php?enzyme_sp=Histone-lysine_N-methyltransferase,_H3_lysine-9_specific_3 |publisher=HIstome: The Histone Infobase |access-date=8 June 2018 |archive-date=12 June 2018 |archive-url=https://web.archive.org/web/20180612135816/http://www.actrec.gov.in/histome/enzyme_sp.php?enzyme_sp=Histone-lysine_N-methyltransferase,_H3_lysine-9_specific_3 |url-status=dead }}</ref><ref name="Histome GLP">{{cite web |title=Histone-lysine N-methyltransferase, H3 lysine-9 specific 5 |url=http://www.actrec.gov.in/histome/enzyme_sp.php?enzyme_sp=Histone-lysine_N-methyltransferase,_H3_lysine-9_specific_5 |publisher=HIstome: The Histone Infobase |access-date=8 June 2018 |archive-date=12 June 2018 |archive-url=https://web.archive.org/web/20180612140934/http://www.actrec.gov.in/histome/enzyme_sp.php?enzyme_sp=Histone-lysine_N-methyltransferase,_H3_lysine-9_specific_5 |url-status=dead }}</ref> G9a is an important control mechanism for [[epigenetic regulation]] within the [[nucleus accumbens]] (NAcc);<ref name="Nestler 2014 epigenetics" /> reduced G9a expression in the NAcc plays a central role in mediating the development of an [[addiction]].<ref name="Nestler 2014 epigenetics" /> G9a opposes increases in [[ΔFosB]] expression via [[H3K9me2]] and is suppressed by ΔFosB.<ref name="Nestler 2014 epigenetics" /><ref name="A feat of epigenetic engineering">{{cite journal | vauthors = Whalley K | title = Psychiatric disorders: a feat of epigenetic engineering | journal = Nature Reviews. Neuroscience | volume = 15 | issue = 12 | pages = 768–9 | date = December 2014 | pmid = 25409693 | doi = 10.1038/nrn3869 | s2cid = 11513288 | doi-access = free }}</ref> G9a exerts opposite effects to that of ΔFosB on drug-related behavior (e.g., [[self-administration]]) and synaptic remodeling (e.g., [[dendritic arborization]] – the development of additional tree-like [[dendrite|dendritic branches]] and [[dendritic spine|spines]]) in the nucleus accumbens, and therefore opposes ΔFosB's function as well as increases in its expression.<ref name="Nestler 2014 epigenetics">{{cite journal | vauthors = Nestler EJ | title = Epigenetic mechanisms of drug addiction | journal = Neuropharmacology | volume = 76 | issue = Pt B | pages = 259–68 | date = January 2014 | pmid = 23643695 | pmc = 3766384 | doi = 10.1016/j.neuropharm.2013.04.004 }}</ref> G9a and ΔFosB share many of the same gene targets.<ref name="Nestler1">{{cite journal | vauthors = Robison AJ, Nestler EJ | title = Transcriptional and epigenetic mechanisms of addiction | journal = Nature Reviews. Neuroscience | volume = 12 | issue = 11 | pages = 623–37 | date = October 2011 | pmid = 21989194 | pmc = 3272277 | doi = 10.1038/nrn3111 }}<br />[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272277/figure/F4/ Figure 4: Epigenetic basis of drug regulation of gene expression]</ref> In addition to its role in the nucleus accumbens, G9a play a critical role in the development and the maintenance of neuropathic pain.<ref name=pmid26551542>{{cite journal |last1=Laumet |first1=Geoffroy |title=G9a is essential for epigenetic silencing of K+ channel genes in acute-to-chronic pain transition |journal=Nature Neuroscience |volume=18 |issue=12 |pages=1746–1755 |doi=10.1038/nn.4165 |pmid=26551542|pmc=4661086 |year=2015 }}</ref><ref>{{cite journal |last1=Liang |first1=Lingli |title=G9a participates in nerve injury-induced Kcna2 downregulation in primary sensory neurons |journal=Scientific Reports |volume=6 |pages=37704 |doi=10.1038/srep37704 |pmid=27874088|pmc=5118693 |year=2016 |bibcode=2016NatSR...637704L }}</ref> Following peripheral nerve injury, G9a regulates the expression of +600 genes in the [[dorsal root ganglia]]. This transcriptomic change reprograms the sensory neurons to a hyperexcitable state leading to mechanical pain hypersensitivity. <ref name=pmid26551542/>
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==References==

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== Interactions ==

EHMT2 has been shown to [[Protein-protein interaction|interact]] with [[KIAA0515]] and the prostate tissue associated homeodomain protein NKX3.1.<ref name=pmid16189514>{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 | bibcode = 2005Natur.437.1173R | s2cid = 4427026 | author-link30 = Huda Zoghbi }}</ref><ref name=pmid27339988>{{cite journal | vauthors = Dutta A et al | title = Identification of an NKX3.1-G9a-UTY transcriptional regulatory network that controls prostate differentiation | journal = Science | volume = 352 | issue = 6293 | pages = 1576–80 | date = June 2016| doi = 10.1126/science.aad9512 | pmid = 27339988 | pmc = 5507586 | bibcode = 2016Sci...352.1576D }}</ref>

== EHMT2 in cancer ==

EHMT2 is known to drive process such as self-renewal and [[Carcinogenesis|tumorigenicity]], and its dysregulation can be associated with cancer. Abnormal EHMT2 expression is found both in haematological malignancies, as for example [[leukemia]], and in [[Neoplasm|solid tumors]], as [[colorectal cancer]], [[lung cancer]], head and neck tumours.<ref>{{Cite journal |last1=Haebe |first1=Joshua R. |last2=Bergin |first2=Christopher J. |last3=Sandouka |first3=Tamara |last4=Benoit |first4=Yannick D. |date=2021-11-13 |title=Emerging role of G9a in cancer stemness and promises as a therapeutic target |journal=Oncogenesis |volume=10 |issue=11 |pages=76 |doi=10.1038/s41389-021-00370-7 |issn=2157-9024 |pmc=8590690 |pmid=34775469}}</ref>

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== References ==
{{reflist}}
{{reflist}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
* {{cite journal | vauthors = Spies T, Bresnahan M, Strominger JL | title = Human major histocompatibility complex contains a minimum of 19 genes between the complement cluster and HLA-B | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 22 | pages = 8955–8 | date = November 1989 | pmid = 2813433 | pmc = 298409 | doi = 10.1073/pnas.86.22.8955 | bibcode = 1989PNAS...86.8955S | doi-access = free }}
{{PBB_Further_reading
* {{cite journal | vauthors = Brown SE, Campbell RD, Sanderson CM | title = Novel NG36/G9a gene products encoded within the human and mouse MHC class III regions | journal = Mammalian Genome | volume = 12 | issue = 12 | pages = 916–24 | date = December 2001 | pmid = 11707778 | doi = 10.1007/s00335-001-3029-3 | s2cid = 9510386 }}
| citations =
*{{cite journal | author=Spies T, Bresnahan M, Strominger JL |title=Human major histocompatibility complex contains a minimum of 19 genes between the complement cluster and HLA-B |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=86 |issue= 22 |pages= 8955–8 |year= 1989 |pmid= 2813433 |doi=10.1073/pnas.86.22.8955 | pmc=298409 }}
* {{cite journal | vauthors = Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y | title = A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells | journal = Science | volume = 296 | issue = 5570 | pages = 1132–6 | date = May 2002 | pmid = 12004135 | doi = 10.1126/science.1069861 | bibcode = 2002Sci...296.1132O | s2cid = 34863978 }}
*{{cite journal | author=Brown SE, Campbell RD, Sanderson CM |title=Novel NG36/G9a gene products encoded within the human and mouse MHC class III regions |journal=Mamm. Genome |volume=12 |issue= 12 |pages= 916–24 |year= 2002 |pmid= 11707778 |doi=10.1007/s00335-001-3029-3 }}
* {{cite journal | vauthors = Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, Ohki M, Fukuda M, Takeda N, Niida H, Kato H, Shinkai Y | title = G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis | journal = Genes & Development | volume = 16 | issue = 14 | pages = 1779–91 | date = July 2002 | pmid = 12130538 | pmc = 186403 | doi = 10.1101/gad.989402 }}
* {{cite journal | vauthors = Shi Y, Sawada J, Sui G, el Affar B, Whetstine JR, Lan F, Ogawa H, Luke MP, Nakatani Y, Shi Y | title = Coordinated histone modifications mediated by a CtBP co-repressor complex | journal = Nature | volume = 422 | issue = 6933 | pages = 735–8 | date = April 2003 | pmid = 12700765 | doi = 10.1038/nature01550 | bibcode = 2003Natur.422..735S | s2cid = 2670859 }}
*{{cite journal | author=Ogawa H |title=A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells |journal=Science |volume=296 |issue= 5570 |pages= 1132–6 |year= 2002 |pmid= 12004135 |doi= 10.1126/science.1069861 | author-separator=, | author2=Ishiguro K | author3=Gaubatz S | display-authors=3 | last4=Livingston | first4=DM | last5=Nakatani | first5=Y }}
* {{cite journal | vauthors = Xie T, Rowen L, Aguado B, Ahearn ME, Madan A, Qin S, Campbell RD, Hood L | title = Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse | journal = Genome Research | volume = 13 | issue = 12 | pages = 2621–36 | date = December 2003 | pmid = 14656967 | pmc = 403804 | doi = 10.1101/gr.1736803 }}
*{{cite journal | author=Tachibana M |title=G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis |journal=Genes Dev. |volume=16 |issue= 14 |pages= 1779–91 |year= 2002 |pmid= 12130538 |doi= 10.1101/gad.989402 | pmc=186403 | author-separator=, | author2=Sugimoto K | author3=Nozaki M | display-authors=3 | last4=Ueda | first4=J | last5=Ohta | first5=T | last6=Ohki | first6=M | last7=Fukuda | first7=M | last8=Takeda | first8=N | last9=Niida | first9=H }}
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* {{cite journal | vauthors = Roopra A, Qazi R, Schoenike B, Daley TJ, Morrison JF | title = Localized domains of G9a-mediated histone methylation are required for silencing of neuronal genes | journal = Molecular Cell | volume = 14 | issue = 6 | pages = 727–38 | date = June 2004 | pmid = 15200951 | doi = 10.1016/j.molcel.2004.05.026 | doi-access = free }}
*{{cite journal | author=Strausberg RL |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 | author-separator=, | author2=Feingold EA | author3=Grouse LH | display-authors=3 | last4=Derge | first4=JG | last5=Klausner | first5=RD | last6=Collins | first6=FS | last7=Wagner | first7=L | last8=Shenmen | first8=CM | last9=Schuler | first9=GD }}
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* {{cite journal | vauthors = Nishio H, Walsh MJ | title = CCAAT displacement protein/cut homolog recruits G9a histone lysine methyltransferase to repress transcription | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 31 | pages = 11257–62 | date = August 2004 | pmid = 15269344 | pmc = 509191 | doi = 10.1073/pnas.0401343101 | bibcode = 2004PNAS..10111257N | doi-access = free }}
*{{cite journal | author=Shi Y |title=Coordinated histone modifications mediated by a CtBP co-repressor complex |journal=Nature |volume=422 |issue= 6933 |pages= 735–8 |year= 2003 |pmid= 12700765 |doi= 10.1038/nature01550 | author-separator=, | author2=Sawada J | author3=Sui G | display-authors=3 | last4=Affar | first4=El Bachir | last5=Whetstine | first5=Johnathan R. | last6=Lan | first6=Fei | last7=Ogawa | first7=Hidesato | last8=Po-Shan Luke | first8=Margaret | last9=Nakatani | first9=Yoshihiro }}
* {{cite journal | vauthors = Collins RE, Tachibana M, Tamaru H, Smith KM, Jia D, Zhang X, Selker EU, Shinkai Y, Cheng X | title = In vitro and in vivo analyses of a Phe/Tyr switch controlling product specificity of histone lysine methyltransferases | journal = The Journal of Biological Chemistry | volume = 280 | issue = 7 | pages = 5563–70 | date = February 2005 | pmid = 15590646 | pmc = 2696276 | doi = 10.1074/jbc.M410483200 | doi-access = free }}
*{{cite journal | author=Xie T |title=Analysis of the Gene-Dense Major Histocompatibility Complex Class III Region and Its Comparison to Mouse |journal=Genome Res. |volume=13 |issue= 12 |pages= 2621–36 |year= 2004 |pmid= 14656967 |doi= 10.1101/gr.1736803 | pmc=403804 | author-separator=, | author2=Rowen L | author3=Aguado B | display-authors=3 | last4=Ahearn | first4=ME | last5=Madan | first5=A | last6=Qin | first6=S | last7=Campbell | first7=RD | last8=Hood | first8=L }}
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* {{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 | bibcode = 2005Natur.437.1173R | s2cid = 4427026 }}
*{{cite journal | author=Ota T |title=Complete sequencing and characterization of 21,243 full-length human cDNAs |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 | author-separator=, | author2=Suzuki Y | author3=Nishikawa T | display-authors=3 | last4=Otsuki | first4=Tetsuji | last5=Sugiyama | first5=Tomoyasu | last6=Irie | first6=Ryotaro | last7=Wakamatsu | first7=Ai | last8=Hayashi | first8=Koji | last9=Sato | first9=Hiroyuki }}
* {{cite journal | vauthors = Duan Z, Zarebski A, Montoya-Durango D, Grimes HL, Horwitz M | title = Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1 | journal = Molecular and Cellular Biology | volume = 25 | issue = 23 | pages = 10338–51 | date = December 2005 | pmid = 16287849 | pmc = 1291230 | doi = 10.1128/MCB.25.23.10338-10351.2005 }}
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*{{cite journal | author=Roopra A |title=Localized domains of G9a-mediated histone methylation are required for silencing of neuronal genes |journal=Mol. Cell |volume=14 |issue= 6 |pages= 727–38 |year= 2005 |pmid= 15200951 |doi= 10.1016/j.molcel.2004.05.026 | author-separator=, | author2=Qazi R | author3=Schoenike B | display-authors=3 | last4=Daley | first4=Timothy J | last5=Morrison | first5=John F }}
* {{cite journal | vauthors = Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S | title = Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes | journal = Genome Research | volume = 16 | issue = 1 | pages = 55–65 | date = January 2006 | pmid = 16344560 | pmc = 1356129 | doi = 10.1101/gr.4039406 }}
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*{{cite journal | author=Nishio H, Walsh MJ |title=CCAAT displacement protein/cut homolog recruits G9a histone lysine methyltransferase to repress transcription |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 31 |pages= 11257–62 |year= 2004 |pmid= 15269344 |doi= 10.1073/pnas.0401343101 | pmc=509191 }}
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* {{cite journal | vauthors = Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP | title = A probability-based approach for high-throughput protein phosphorylation analysis and site localization | journal = Nature Biotechnology | volume = 24 | issue = 10 | pages = 1285–92 | date = October 2006 | pmid = 16964243 | doi = 10.1038/nbt1240 | s2cid = 14294292 }}
*{{cite journal | author=Gerhard DS |title=The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 | author-separator=, | author2=Wagner L | author3=Feingold EA | display-authors=3 | last4=Shenmen | first4=CM | last5=Grouse | first5=LH | last6=Schuler | first6=G | last7=Klein | first7=SL | last8=Old | first8=S | last9=Rasooly | first9=R }}
* {{cite journal | vauthors = Reeves M, Murphy J, Greaves R, Fairley J, Brehm A, Sinclair J | title = Autorepression of the human cytomegalovirus major immediate-early promoter/enhancer at late times of infection is mediated by the recruitment of chromatin remodeling enzymes by IE86 | journal = Journal of Virology | volume = 80 | issue = 20 | pages = 9998–10009 | date = October 2006 | pmid = 17005678 | pmc = 1617317 | doi = 10.1128/JVI.01297-06 }}
*{{cite journal | author=Collins RE |title=In Vitro and in Vivo Analyses of a Phe/Tyr Switch Controlling Product Specificity of Histone Lysine Methyltransferases |journal=J. Biol. Chem. |volume=280 |issue= 7 |pages= 5563–70 |year= 2005 |pmid= 15590646 |doi= 10.1074/jbc.M410483200 | pmc=2696276 | author-separator=, | author2=Tachibana M | author3=Tamaru H | display-authors=3 | last4=Smith | first4=KM | last5=Jia | first5=D | last6=Zhang | first6=X | last7=Selker | first7=EU | last8=Shinkai | first8=Y | last9=Cheng | first9=X }}
* {{cite journal | vauthors = Estève PO, Chin HG, Smallwood A, Feehery GR, Gangisetty O, Karpf AR, Carey MF, Pradhan S | title = Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication | journal = Genes & Development | volume = 20 | issue = 22 | pages = 3089–103 | date = November 2006 | pmid = 17085482 | pmc = 1635145 | doi = 10.1101/gad.1463706 }}
*{{cite journal | author=Rual JF |title=Towards a proteome-scale map of the human protein-protein interaction network |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 | author-separator=, | author2=Venkatesan K | author3=Hao T | display-authors=3 | last4=Hirozane-Kishikawa | first4=Tomoko | last5=Dricot | first5=Amélie | last6=Li | first6=Ning | last7=Berriz | first7=Gabriel F. | last8=Gibbons | first8=Francis D. | last9=Dreze | first9=Matija }}
*{{cite journal | author=Duan Z |title=Gfi1 Coordinates Epigenetic Repression of p21Cip/WAF1 by Recruitment of Histone Lysine Methyltransferase G9a and Histone Deacetylase 1 |journal=Mol. Cell. Biol. |volume=25 |issue= 23 |pages= 10338–51 |year= 2005 |pmid= 16287849 |doi= 10.1128/MCB.25.23.10338-10351.2005 | pmc=1291230 | author-separator=, | author2=Zarebski A | author3=Montoya-Durango D | display-authors=3 | last4=Grimes | first4=H. L. | last5=Horwitz | first5=M. }}
*{{cite journal | author=Kimura K |title=Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes |journal=Genome Res. |volume=16 |issue= 1 |pages= 55–65 |year= 2006 |pmid= 16344560 |doi= 10.1101/gr.4039406 | pmc=1356129 | author-separator=, | author2=Wakamatsu A | author3=Suzuki Y | display-authors=3 | last4=Ota | first4=T | last5=Nishikawa | first5=T | last6=Yamashita | first6=R | last7=Yamamoto | first7=J | last8=Sekine | first8=M | last9=Tsuritani | first9=K }}
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*{{cite journal | author=Beausoleil SA |title=A probability-based approach for high-throughput protein phosphorylation analysis and site localization |journal=Nat. Biotechnol. |volume=24 |issue= 10 |pages= 1285–92 |year= 2006 |pmid= 16964243 |doi= 10.1038/nbt1240 | author-separator=, | author2=Villén J | author3=Gerber SA | display-authors=3 | last4=Rush | first4=John | last5=Gygi | first5=Steven P }}
*{{cite journal | author=Reeves M |title=Autorepression of the Human Cytomegalovirus Major Immediate-Early Promoter/Enhancer at Late Times of Infection Is Mediated by the Recruitment of Chromatin Remodeling Enzymes by IE86 |journal=J. Virol. |volume=80 |issue= 20 |pages= 9998–10009 |year= 2006 |pmid= 17005678 |doi= 10.1128/JVI.01297-06 | pmc=1617317 | author-separator=, | author2=Murphy J | author3=Greaves R | display-authors=3 | last4=Fairley | first4=J. | last5=Brehm | first5=A. | last6=Sinclair | first6=J. }}
*{{cite journal | author=Estève PO |title=Direct interaction between DNMT1and G9a coordinates DNA and histone methylation during replication |journal=Genes Dev. |volume=20 |issue= 22 |pages= 3089–103 |year= 2006 |pmid= 17085482 |doi= 10.1101/gad.1463706 | pmc=1635145 | author-separator=, | author2=Chin HG | author3=Smallwood A | display-authors=3 | last4=Feehery | first4=G. R. | last5=Gangisetty | first5=O. | last6=Karpf | first6=A. R. | last7=Carey | first7=M. F. | last8=Pradhan | first8=S. }}
}}
{{refend}}
{{refend}}
{{PDB Gallery|geneid=10919}}


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Latest revision as of 12:00, 22 June 2024

EHMT2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesEHMT2, BAT8, C6orf30, G9A, GAT8, KMT1C, NG36, euchromatic histone lysine methyltransferase 2
External IDsOMIM: 604599; MGI: 2148922; HomoloGene: 48460; GeneCards: EHMT2; OMA:EHMT2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

10919

110147

Ensembl

ENSMUSG00000013787

UniProt

Q96KQ7

Q9Z148

RefSeq (mRNA)

NM_001286573
NM_001286575
NM_145830
NM_147151

RefSeq (protein)

NP_001276342
NP_001305762
NP_006700
NP_079532
NP_001350618

Location (UCSC)Chr 6: 31.88 – 31.9 MbChr 17: 35.12 – 35.13 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Euchromatic histone-lysine N-methyltransferase 2 (EHMT2), also known as G9a, is a histone methyltransferase enzyme that in humans is encoded by the EHMT2 gene.[5][6][7] G9a deposits the mono- and di-methylated states of histone H3 at lysine residue 9 (i.e., H3K9me1 and H3K9me2) and lysine residue 27 (H3K27me1 and H3K27me2).[8][9] The presence of H3K9me1/2 is usually associated with gene silencing.

Function

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A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. This gene is found near this cluster; it was mapped near the gene for C2 within a 120-kb region that included a HSP70 gene pair. These genes are all within the human major histocompatibility complex class III region. This gene was thought to be two different genes, NG36 and G9a, adjacent to each other but a recent publication shows that there is only a single gene. The protein encoded by this gene is thought to be involved in intracellular protein-protein interaction. There are three alternatively spliced transcript variants of this gene but only two are fully described.[7]

G9a and G9a-like protein, another histone-lysine N-methyltransferase, catalyze the synthesis of H3K9me2, which is a repressive mark.[8][9][10] G9a is an important control mechanism for epigenetic regulation within the nucleus accumbens (NAcc);[11] reduced G9a expression in the NAcc plays a central role in mediating the development of an addiction.[11] G9a opposes increases in ΔFosB expression via H3K9me2 and is suppressed by ΔFosB.[11][12] G9a exerts opposite effects to that of ΔFosB on drug-related behavior (e.g., self-administration) and synaptic remodeling (e.g., dendritic arborization – the development of additional tree-like dendritic branches and spines) in the nucleus accumbens, and therefore opposes ΔFosB's function as well as increases in its expression.[11] G9a and ΔFosB share many of the same gene targets.[13] In addition to its role in the nucleus accumbens, G9a play a critical role in the development and the maintenance of neuropathic pain.[14][15] Following peripheral nerve injury, G9a regulates the expression of +600 genes in the dorsal root ganglia. This transcriptomic change reprograms the sensory neurons to a hyperexcitable state leading to mechanical pain hypersensitivity. [14]

Interactions

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EHMT2 has been shown to interact with KIAA0515 and the prostate tissue associated homeodomain protein NKX3.1.[16][17]

EHMT2 in cancer

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EHMT2 is known to drive process such as self-renewal and tumorigenicity, and its dysregulation can be associated with cancer. Abnormal EHMT2 expression is found both in haematological malignancies, as for example leukemia, and in solid tumors, as colorectal cancer, lung cancer, head and neck tumours.[18]

References

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  1. ^ a b c ENSG00000224143, ENSG00000206376, ENSG00000204371, ENSG00000227333, ENSG00000232045, ENSG00000236759 GRCh38: Ensembl release 89: ENSG00000238134, ENSG00000224143, ENSG00000206376, ENSG00000204371, ENSG00000227333, ENSG00000232045, ENSG00000236759 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000013787 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Milner CM, Campbell RD (March 1993). "The G9a gene in the human major histocompatibility complex encodes a novel protein containing ankyrin-like repeats". The Biochemical Journal. 290 (Pt 3): 811–8. doi:10.1042/bj2900811. PMC 1132354. PMID 8457211.
  6. ^ Tachibana M, Sugimoto K, Fukushima T, Shinkai Y (July 2001). "Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3". The Journal of Biological Chemistry. 276 (27): 25309–17. doi:10.1074/jbc.M101914200. PMID 11316813.
  7. ^ a b "Entrez Gene: EHMT2 euchromatic histone-lysine N-methyltransferase 2".
  8. ^ a b Nestler EJ (August 2015). Role of the Brain's Reward Circuitry in Depression: Transcriptional Mechanisms. Vol. 124. pp. 151–70. doi:10.1016/bs.irn.2015.07.003. ISBN 9780128015834. PMC 4690450. PMID 26472529. {{cite book}}: |journal= ignored (help)
  9. ^ a b "Histone-lysine N-methyltransferase, H3 lysine-9 specific 3". HIstome: The Histone Infobase. Archived from the original on 12 June 2018. Retrieved 8 June 2018.
  10. ^ "Histone-lysine N-methyltransferase, H3 lysine-9 specific 5". HIstome: The Histone Infobase. Archived from the original on 12 June 2018. Retrieved 8 June 2018.
  11. ^ a b c d Nestler EJ (January 2014). "Epigenetic mechanisms of drug addiction". Neuropharmacology. 76 (Pt B): 259–68. doi:10.1016/j.neuropharm.2013.04.004. PMC 3766384. PMID 23643695.
  12. ^ Whalley K (December 2014). "Psychiatric disorders: a feat of epigenetic engineering". Nature Reviews. Neuroscience. 15 (12): 768–9. doi:10.1038/nrn3869. PMID 25409693. S2CID 11513288.
  13. ^ Robison AJ, Nestler EJ (October 2011). "Transcriptional and epigenetic mechanisms of addiction". Nature Reviews. Neuroscience. 12 (11): 623–37. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194.
    Figure 4: Epigenetic basis of drug regulation of gene expression
  14. ^ a b Laumet, Geoffroy (2015). "G9a is essential for epigenetic silencing of K+ channel genes in acute-to-chronic pain transition". Nature Neuroscience. 18 (12): 1746–1755. doi:10.1038/nn.4165. PMC 4661086. PMID 26551542.
  15. ^ Liang, Lingli (2016). "G9a participates in nerve injury-induced Kcna2 downregulation in primary sensory neurons". Scientific Reports. 6: 37704. Bibcode:2016NatSR...637704L. doi:10.1038/srep37704. PMC 5118693. PMID 27874088.
  16. ^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
  17. ^ Dutta A, et al. (June 2016). "Identification of an NKX3.1-G9a-UTY transcriptional regulatory network that controls prostate differentiation". Science. 352 (6293): 1576–80. Bibcode:2016Sci...352.1576D. doi:10.1126/science.aad9512. PMC 5507586. PMID 27339988.
  18. ^ Haebe, Joshua R.; Bergin, Christopher J.; Sandouka, Tamara; Benoit, Yannick D. (13 November 2021). "Emerging role of G9a in cancer stemness and promises as a therapeutic target". Oncogenesis. 10 (11): 76. doi:10.1038/s41389-021-00370-7. ISSN 2157-9024. PMC 8590690. PMID 34775469.

Further reading

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