[{"@context":"http:\/\/schema.org\/","@type":"BlogPosting","@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/prdm9-wikipedia\/#BlogPosting","mainEntityOfPage":"https:\/\/wiki.edu.vn\/en\/wiki24\/prdm9-wikipedia\/","headline":"PRDM9 &#8211; Wikipedia","name":"PRDM9 &#8211; Wikipedia","description":"From Wikipedia, the free encyclopedia Protein-coding gene in humans PR domain[note 1] zinc finger protein 9 is a protein that","datePublished":"2021-11-06","dateModified":"2021-11-06","author":{"@type":"Person","@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/author\/lordneo\/#Person","name":"lordneo","url":"https:\/\/wiki.edu.vn\/en\/wiki24\/author\/lordneo\/","image":{"@type":"ImageObject","@id":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","height":96,"width":96}},"publisher":{"@type":"Organization","name":"Enzyklop\u00e4die","logo":{"@type":"ImageObject","@id":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","url":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","width":600,"height":60}},"image":{"@type":"ImageObject","@id":"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/a\/a6\/PRDM9_Domain_Architecture.png\/220px-PRDM9_Domain_Architecture.png","url":"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/a\/a6\/PRDM9_Domain_Architecture.png\/220px-PRDM9_Domain_Architecture.png","height":"35","width":"220"},"url":"https:\/\/wiki.edu.vn\/en\/wiki24\/prdm9-wikipedia\/","about":["Wiki"],"wordCount":10768,"articleBody":"From Wikipedia, the free encyclopediaProtein-coding gene in humansPR domain[note 1] zinc finger protein 9 is a protein that in humans is encoded by the PRDM9 gene.[5] PRDM9 is responsible for positioning recombination hotspots during meiosis by binding a DNA sequence motif encoded in its zinc finger domain.[6] PRDM9 is the only speciation gene found so far in mammals, and is one of the fastest evolving genes in the genome.[7][8]Table of ContentsDomain Architecture[edit]History[edit]Function in Recombination[edit]References[edit]Further reading[edit]External links[edit]Domain Architecture[edit]  Schematic of the PRDM9 Domain Architecture in micePRDM9 has multiple domains including KRAB domain, SSXRD, PR\/SET domain (H3K4 &#038; H3K36 trimethyltransferase), and an array of C2H2 Zinc Finger domains (DNA binding).[9]History[edit]In 1974 Jiri Forejt and P. Ivanyi identified a locus which they named Hst1 which controlled hybrid sterility.[10]In 1982 a haplotype was identified controlling recombination rate wm7,[11] which would later be identified as PRDM9.[12]In 1991 a protein binding to the minisatelite consensus sequence 5\u2032-CCACCTGCCCACCTCT-3\u2032 was detected and partially purified (named Msbp3 &#8211; minisatelite binding protein 3).[13] This would later turn out to be the same PRDM9 protein independently identified later.[14]In 2005 a gene was identified (named Meisetz) that is required for progression through meiotic prophase and has H3K4 methyltransferase activity.[15]In 2009 Jiri Forejt and colleagues identified Hst1 as Meisetz\/PRDM9 &#8211; the first and so far only speciation gene in mammals.[16]Later in 2009 PRDM9 was identified as one of the fastest evolving genes in the genome.[9][17]In 2010 three groups independently identified PRDM9 as controlling the positioning of recombination hotspots in humans and mice.[6][18][19][20][21]in 2012 it was shown that almost all hotspots are positioned by PRDM9 and that in its absence hotspots form near promoters.[22]In 2014 it was reported that the PRDM9 SET domain could also trimethylate H3K36 in vitro,[23] which was confirmed in vivo in 2016.[24]In 2016 it was shown that the hybrid sterility caused by PRDM9 can be reversed and that the sterility is caused by asymmetric double strand breaks.[25][26]Function in Recombination[edit]PRDM9 mediates the process of meiosis by directing the sites of homologous recombination.[27] In humans and mice, recombination does not occur evenly throughout the genome but at particular sites along the chromosomes called recombination hotspots.  Hotspots are regions of DNA about 1-2kb in length.[28]  There are approximately 30,000 to 50,000 hotspots within the human genome corresponding to one for every 50-100kb DNA on average.[28]  In humans, the average number of crossover recombination events per hotspot is one per 1,300 meioses, and the most extreme hotspot has a crossover frequency of one per 110 meioses.[28]  These hotspots are binding sites for the PRDM9 Zinc Finger array.[29] Upon binding to DNA, PRDM9 catalyzes trimethylation of Histone 3 at lysine 4 and lysine 36.[30] As a result, local nucleosomes are reorganized and through an unknown mechanism the recombination machinery is recruited to form double strand breaks.^ positive-regulatory domainReferences[edit]^ a b c GRCh38: Ensembl release 89: ENSG00000164256 &#8211; Ensembl, May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000051977 &#8211; Ensembl, May 2017^ &#8220;Human PubMed Reference:&#8221;. National Center for Biotechnology Information, U.S. National Library of Medicine.^ &#8220;Mouse PubMed Reference:&#8221;. National Center for Biotechnology Information, U.S. National Library of Medicine.^ &#8220;Entrez Gene: PR domain containing 9&#8221;.^ a b Cheung VG, Sherman SL, Feingold E (February 2010). &#8220;Genetics. Genetic control of hotspots&#8221;. Science. 327 (5967): 791\u20132. doi:10.1126\/science.1187155. PMID\u00a020150474. S2CID\u00a0206525444.^ &#8220;There are millions of different species worldwide. But how do new species first appear, and then remain separate?&#8221;. royalsociety.org-gb. Retrieved 2017-12-10.^ Ponting CP (May 2011). &#8220;What are the genomic drivers of the rapid evolution of PRDM9?&#8221;. Trends in Genetics. 27 (5): 165\u201371. doi:10.1016\/j.tig.2011.02.001. PMID\u00a021388701.^ a b Thomas JH, Emerson RO, Shendure J (December 2009). &#8220;Extraordinary molecular evolution in the PRDM9 fertility gene&#8221;. PLOS ONE. 4 (12): e8505. Bibcode:2009PLoSO&#8230;4.8505T. doi:10.1371\/journal.pone.0008505. PMC\u00a02794550. PMID\u00a020041164. ^ Forejt J, Iv\u00e1nyi P (1974). &#8220;Genetic studies on male sterility of hybrids between laboratory and wild mice (Mus musculus L.)&#8221;. Genetical Research. 24 (2): 189\u2013206. doi:10.1017\/S0016672300015214. PMID\u00a04452481.^ Shiroishi T, Sagai T, Moriwaki K (1982). &#8220;A new wild-derived H-2 haplotype enhancing K-IA recombination&#8221;. Nature. 300 (5890): 370\u20132. Bibcode:1982Natur.300..370S. doi:10.1038\/300370a0. PMID\u00a06815537. S2CID\u00a04370624.^ Kono H, Tamura M, Osada N, Suzuki H, Abe K, Moriwaki K, Ohta K, Shiroishi T (June 2014). &#8220;Prdm9 polymorphism unveils mouse evolutionary tracks&#8221;. DNA Research. 21 (3): 315\u201326. doi:10.1093\/dnares\/dst059. PMC\u00a04060951. PMID\u00a024449848.^ Wahls WP, Swenson G, Moore PD (June 1991). &#8220;Two hypervariable minisatellite DNA binding proteins&#8221;. Nucleic Acids Research. 19 (12): 3269\u201374. doi:10.1093\/nar\/19.12.3269. PMC\u00a0328321. PMID\u00a02062643.^ Wahls WP, Davidson MK (November 2011). &#8220;DNA sequence-mediated, evolutionarily rapid redistribution of meiotic recombination hotspots&#8221;. Genetics. 189 (3): 685\u201394. doi:10.1534\/genetics.111.134130. PMC\u00a03213376. PMID\u00a022084420.^ Hayashi K, Yoshida K, Matsui Y (November 2005). &#8220;A histone H3 methyltransferase controls epigenetic events required for meiotic prophase&#8221;. Nature. 438 (7066): 374\u20138. Bibcode:2005Natur.438..374H. doi:10.1038\/nature04112. PMID\u00a016292313. S2CID\u00a04412934.^ Mihola O, Trachtulec Z, Vlcek C, Schimenti JC, Forejt J (January 2009). &#8220;A mouse speciation gene encodes a meiotic histone H3 methyltransferase&#8221;. Science. 323 (5912): 373\u20135. Bibcode:2009Sci&#8230;323..373M. CiteSeerX\u00a010.1.1.363.6020. doi:10.1126\/science.1163601. PMID\u00a019074312. S2CID\u00a01065925.^ Oliver PL, Goodstadt L, Bayes JJ, Birtle Z, Roach KC, Phadnis N, Beatson SA, Lunter G, Malik HS, Ponting CP (December 2009). &#8220;Accelerated evolution of the Prdm9 speciation gene across diverse metazoan taxa&#8221;. PLOS Genetics. 5 (12): e1000753. doi:10.1371\/journal.pgen.1000753. PMC\u00a02779102. PMID\u00a019997497.^ Neale MJ (2010-02-26). &#8220;PRDM9 points the zinc finger at meiotic recombination hotspots&#8221;. Genome Biology. 11 (2): 104. doi:10.1186\/gb-2010-11-2-104. PMC\u00a02872867. PMID\u00a020210982.^ Myers S, Bowden R, Tumian A, Bontrop RE, Freeman C, MacFie TS, McVean G, Donnelly P (February 2010). &#8220;Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination&#8221;. Science. 327 (5967): 876\u20139. Bibcode:2010Sci&#8230;327..876M. doi:10.1126\/science.1182363. PMC\u00a03828505. PMID\u00a020044541.^ Baudat F, Buard J, Grey C, Fledel-Alon A, Ober C, Przeworski M, Coop G, de Massy B (February 2010). &#8220;PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice&#8221;. Science. 327 (5967): 836\u201340. Bibcode:2010Sci&#8230;327..836B. doi:10.1126\/science.1183439. PMC\u00a04295902. PMID\u00a020044539.^ Parvanov ED, Petkov PM, Paigen K (February 2010). &#8220;Prdm9 controls activation of mammalian recombination hotspots&#8221;. Science. 327 (5967): 835. Bibcode:2010Sci&#8230;327..835P. doi:10.1126\/science.1181495. PMC\u00a02821451. PMID\u00a020044538.^ Brick K, Smagulova F, Khil P, Camerini-Otero RD, Petukhova GV (May 2012). &#8220;Genetic recombination is directed away from functional genomic elements in mice&#8221;. Nature. 485 (7400): 642\u20135. Bibcode:2012Natur.485..642B. doi:10.1038\/nature11089. PMC\u00a03367396. PMID\u00a022660327.^ Eram MS, Bustos SP, Lima-Fernandes E, Siarheyeva A, Senisterra G, Hajian T, Chau I, Duan S, Wu H, Dombrovski L, Schapira M, Arrowsmith CH, Vedadi M (April 2014). &#8220;Trimethylation of histone H3 lysine 36 by human methyltransferase PRDM9 protein&#8221;. The Journal of Biological Chemistry. 289 (17): 12177\u201388. doi:10.1074\/jbc.M113.523183. PMC\u00a04002121. PMID\u00a024634223.^ Powers NR, Parvanov ED, Baker CL, Walker M, Petkov PM, Paigen K (June 2016). &#8220;The Meiotic Recombination Activator PRDM9 Trimethylates Both H3K36 and H3K4 at Recombination Hotspots In Vivo&#8221;. PLOS Genetics. 12 (6): e1006146. doi:10.1371\/journal.pgen.1006146. PMC\u00a04928815. PMID\u00a027362481.^ Davies B, Hatton E, Altemose N, Hussin JG, Pratto F, Zhang G, Hinch AG, Moralli D, Biggs D, Diaz R, Preece C, Li R, Bitoun E, Brick K, Green CM, Camerini-Otero RD, Myers SR, Donnelly P (February 2016). &#8220;Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice&#8221;. Nature. 530 (7589): 171\u2013176. Bibcode:2016Natur.530..171D. doi:10.1038\/nature16931. PMC\u00a04756437. PMID\u00a026840484.^ Forejt J (February 2016). &#8220;Genetics: Asymmetric breaks in DNA cause sterility&#8221;. Nature. 530 (7589): 167\u20138. Bibcode:2016Natur.530..167F. doi:10.1038\/nature16870. PMID\u00a026840487.^ Smagulova F, Gregoretti IV, Brick K, Khil P, Camerini-Otero RD, Petukhova GV (April 2011). &#8220;Genome-wide analysis reveals novel molecular features of mouse recombination hotspots&#8221;. Nature. 472 (7343): 375\u20138. Bibcode:2011Natur.472..375S. doi:10.1038\/nature09869. PMC\u00a03117304. PMID\u00a021460839.^ a b c ^ de Massy B (November 2014). &#8220;Human genetics. Hidden features of human hotspots&#8221;. Science. 346 (6211): 808\u20139. doi:10.1126\/science.aaa0612. PMID\u00a025395519. S2CID\u00a0195680901.^ Powers, NR; Parvanov, ED; Baker, CL; Walker, M; Petkov, PM; Paigen, K (June 2016). &#8220;The Meiotic Recombination Activator PRDM9 Trimethylates Both H3K36 and H3K4 at Recombination Hotspots In Vivo&#8221;. PLOS Genetics. 12 (6): e1006146. doi:10.1371\/journal.pgen.1006146. PMC\u00a04928815. PMID\u00a027362481.Further reading[edit]Baudat F, Buard J, Grey C, Fledel-Alon A, Ober C, Przeworski M, Coop G, de Massy B (February 2010). &#8220;PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice&#8221;. Science. 327 (5967): 836\u201340. Bibcode:2010Sci&#8230;327..836B. doi:10.1126\/science.1183439. PMC\u00a04295902. PMID\u00a020044539.Berg IL, Neumann R, Lam KW, Sarbajna S, Odenthal-Hesse L, May CA, Jeffreys AJ (October 2010). &#8220;PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans&#8221;. Nature Genetics. 42 (10): 859\u201363. doi:10.1038\/ng.658. PMC\u00a03092422. PMID\u00a020818382.Irie S, Tsujimura A, Miyagawa Y, Ueda T, Matsuoka Y, Matsui Y, Okuyama A, Nishimune Y, Tanaka H (2009). &#8220;Single-nucleotide polymorphisms of the PRDM9 (MEISETZ) gene in patients with nonobstructive azoospermia&#8221;. Journal of Andrology. 30 (4): 426\u201331. doi:10.2164\/jandrol.108.006262. PMID\u00a019168450.Sun XJ, Xu PF, Zhou T, Hu M, Fu CT, Zhang Y, Jin Y, Chen Y, Chen SJ, Huang QH, Liu TX, Chen Z (January 2008). &#8220;Genome-wide survey and developmental expression mapping of zebrafish SET domain-containing genes&#8221;. PLOS ONE. 3 (1): e1499. Bibcode:2008PLoSO&#8230;3.1499S. doi:10.1371\/journal.pone.0001499. PMC\u00a02200798. PMID\u00a018231586.Xiao B, Wilson JR, Gamblin SJ (December 2003). &#8220;SET domains and histone methylation&#8221;. Current Opinion in Structural Biology. 13 (6): 699\u2013705. doi:10.1016\/j.sbi.2003.10.003. PMID\u00a014675547.Wahls WP, Swenson G, Moore PD (June 1991). &#8220;Two hypervariable minisatellite DNA binding proteins&#8221;. Nucleic Acids Research. 19 (12): 3269\u201374. doi:10.1093\/nar\/19.12.3269. PMC\u00a0328321. PMID\u00a02062643.Jiang GL, Huang S (January 2000). &#8220;The yin-yang of PR-domain family genes in tumorigenesis&#8221;. Histology and Histopathology. 15 (1): 109\u201317. PMID\u00a010668202.Parvanov ED, Petkov PM, Paigen K (February 2010). &#8220;Prdm9 controls activation of mammalian recombination hotspots&#8221;. Science. 327 (5967): 835. Bibcode:2010Sci&#8230;327..835P. doi:10.1126\/science.1181495. PMC\u00a02821451. PMID\u00a020044538.Myers S, Bowden R, Tumian A, Bontrop RE, Freeman C, MacFie TS, McVean G, Donnelly P (February 2010). &#8220;Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination&#8221;. Science. 327 (5967): 876\u20139. Bibcode:2010Sci&#8230;327..876M. doi:10.1126\/science.1182363. PMC\u00a03828505. PMID\u00a020044541.Miyamoto T, Koh E, Sakugawa N, Sato H, Hayashi H, Namiki M, Sengoku K (2008). &#8220;Two single nucleotide polymorphisms in PRDM9 (MEISETZ) gene may be a genetic risk factor for Japanese patients with azoospermia by meiotic arrest&#8221;. Journal of Assisted Reproduction and Genetics. 25 (11\u201312): 553\u20137. doi:10.1007\/s10815-008-9270-x. PMC\u00a02593767. PMID\u00a018941885.Hussin J, Sinnett D, Casals F, Idaghdour Y, Bruat V, Saillour V, Healy J, Grenier JC, de Malliard T, Busche S, Spinella JF, Larivi\u00e8re M, Gibson G, Andersson A, Holmfeldt L, Ma J, Wei L, Zhang J, Andelfinger G, Downing JR, Mullighan CG, Awadalla P (March 2013). &#8220;Rare allelic forms of PRDM9 associated with childhood leukemogenesis&#8221;. Genome Research. 23 (3): 419\u201330. doi:10.1101\/gr.144188.112. PMC\u00a03589531. PMID\u00a023222848.External links[edit]This article incorporates text from the United States National Library of Medicine, which is in the public domain.  "},{"@context":"http:\/\/schema.org\/","@type":"BreadcrumbList","itemListElement":[{"@type":"ListItem","position":1,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/#breadcrumbitem","name":"Enzyklop\u00e4die"}},{"@type":"ListItem","position":2,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/prdm9-wikipedia\/#breadcrumbitem","name":"PRDM9 &#8211; Wikipedia"}}]}]