DMRT1 is a dose sensitive transcription factor protein that regulates Sertoli cells and germ cells. The DMRT1 gene is located at the end of the 9th chromosome. This gene is found in a cluster with two other members of the gene family, having in common a zinc finger-like DNA-binding motif (DM domain). The DM domain is an ancient, conserved component of the vertebrate sex-determining pathway that is also a key regulator of male development in flies and nematodes, and is found to be the key sex-determining factor in chickens.[8] The majority of DMRT1 protein is located in the testicular cord and Sertoli cells, with a small amount in the germ cells.
Defective testicular development and XY feminization occur when this gene is hemizygous.[5] Two copies of the DMRT1 gene are required for normal sexual development. When a DMRT1 gene is lost, the most common disease is chromosome 9p deletion, which causes abnormal testicular formation and feminization. The DMRT1 gene is critical for male sex determination; without this gene the female characteristic takes over and male characteristic is slight or non-existent.
When DMRT1 is knocked out in mice, the mice showed changes in both Sertoli and germ cells soon after formation of the gonadal ridge. The main defects associated with DMRT1 knockout were developmental arrest, excess proliferation of germ cells, and failure to undergo meiosis, mitosis, or migration. Thus, the knockout model shows that loss of the DMRT1 gene is associated with incomplete germ cell development leading to infertility, abnormal testicular formation, and/or feminization of the affected individual.[citation needed] Induced knockout of DMRT1 in adult male mice has been found to cause transdifferentiation of somatic cells in the testis to the equivalent cell types that would ordinarily be found in the ovary.[9] Conversely, conditional expression of DMRT1 in the gonad of female mice caused the apparent transdifferentiation of ovarian somatic (granulosa) cells to the equivalent cell type (Sertoli) ordinarily found in males.[10]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000137090 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000024837 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ab"Entrez Gene: DMRT1 doublesex and mab-3 related transcription factor 1".
^Raymond CS, Shamu CE, Shen MM, Seifert KJ, Hirsch B, Hodgkin J, Zarkower D (February 1998). "Evidence for evolutionary conservation of sex-determining genes". Nature. 391 (6668): 691–5. Bibcode:1998Natur.391..691R. doi:10.1038/35618. PMID 9490411. S2CID 11414843.
^Raymond CS, Parker ED, Kettlewell JR, Brown LG, Page DC, Kusz K, Jaruzelska J, Reinberg Y, Flejter WL, Bardwell VJ, Hirsch B, Zarkower D (June 1999). "A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators". Hum. Mol. Genet. 8 (6): 989–96. doi:10.1093/hmg/8.6.989. PMID 10332030.
^Smith CA, Roeszler KN, Ohnesorg T, Cummins DM, Farlie PG, Doran TJ, Sinclair AH (August 2009). "The avian Z-linked gene DMRT1 is required for male sex determination in the chicken". Nature. 461 (7261): 267–71. Bibcode:2009Natur.461..267S. doi:10.1038/nature08298. PMID 19710650. S2CID 4413389.
^Lindeman RE, Gearhart MD, Minkina A, Krentz AD, Bardwell VJ, Zarkower D (March 2015). "Sexual cell-fate reprogramming in the ovary by DMRT1". Curr Biol. 25 (6): 764–71. Bibcode:2015CBio...25..764L. doi:10.1016/j.cub.2015.01.034. PMC4366330. PMID 25683803.
Anthony D. Krentza,b, Mark W. Murphya, Shinseog Kima,1, Matthew S. Cookc, Blanche Capelc, Rui Zhud, Angabin Matind, Aaron L. Sarvere, Keith L. Parkerf, Michael D. Griswoldg, Leendert H. J. Looijengah, Vivian J. Bardwella and David Zarkower. "The DM Domain Protein DMRT1 Is a Dose-sensitive Regulator of Fetal Germ Cell Proliferation and Pluripotency." The DM Domain Protein DMRT1 Is a Dose-sensitive Regulator of Fetal Germ Cell Proliferation and Pluripotency. PNAS, 29 Oct. 2009. Web. 12 Mar. 2014.
Christopher S. Raymond1, Emily D. Parker2, Jae R. Kettlewell1, Laura G. Brown3, David C. Page3, Kamila Kusz4, Jadwiga Jaruzelska4, Yuri Reinberg5, Wendy L. Flejter6, Vivian J. Bardwell1,2, Betsy Hirsch7 and David Zarkower1. "Human Molecular Genetics." A Region of Human Chromosome 9p Required for Testis Development Contains Two Genes Related to Known Sexual Regulators. Oxford Journal, n.d. Web. 28 Feb. 2014.
Craig A. Smith, Kelly N. Roeszler, Thomas Ohnesorg, David M. Cummins, Peter G. Farlie, Timothy J. Doran & Andrew H. Sinclair. "The Avian Z-linked Gene DMRT1 Is Required for Male Sex Determination in the Chicken." Nature.com. Nature, 26 Aug. 2009. Web. 12 Mar. 2014.
"DMRT1 Gene." - GeneCards. Crown Human Genome Center, Department of Molecular Genetics, the Weizmann Institute of Science,http://genome.ucsc.edu/. 23 Oct. 2013. Web. 12 Mar. 2014.
Ning Lei, Kaori I. Hornbaker, Daren A. Rice, Tatiana Karpova, Valentine A. Agbor, and Leslie L. Heckert. "Sex-specific Differences in Mouse DMRT1 Expression Are Both Cell Type- and Stage-dependent during Gonad Development." Sex-specific Differences in Mouse DMRT1 Expression Are Both Cell Type- and Stage-dependent during Gonad Development. NIH Public Access, 13 June 2007. Web. 12 Mar. 2014.
Further readingedit
Smith CA, McClive PJ, Western PS, et al. (2000). "Conservation of a sex-determining gene". Nature. 402 (6762): 601–2. doi:10.1038/45127. PMID 10604464. S2CID 4401771.
Calvari V, Bertini V, De Grandi A, et al. (2000). "A new submicroscopic deletion that refines the 9p region for sex reversal". Genomics. 65 (3): 203–12. doi:10.1006/geno.2000.6160. PMID 10857744.
Muroya K, Okuyama T, Goishi K, et al. (2000). "Sex-determining gene(s) on distal 9p: clinical and molecular studies in six cases". J. Clin. Endocrinol. Metab. 85 (9): 3094–100. doi:10.1210/jcem.85.9.6771. PMID 10999792. S2CID 22145136.
Raymond CS, Murphy MW, O'Sullivan MG, et al. (2000). "Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation". Genes Dev. 14 (20): 2587–95. doi:10.1101/gad.834100. PMC316999. PMID 11040213.
Casci T (2001). "It's a guy thing". Nat. Rev. Genet. 1 (3): 169. doi:10.1038/35042034. PMID 11252745. S2CID 205010812.
Harrington JJ, Sherf B, Rundlett S, et al. (2001). "Creation of genome-wide protein expression libraries using random activation of gene expression". Nat. Biotechnol. 19 (5): 440–5. doi:10.1038/88107. PMID 11329013. S2CID 25064683.
Boyer A, Dornan S, Daneau I, et al. (2004). "Conservation of the function of DMRT1 regulatory sequences in mammalian sex differentiation". Genesis. 34 (4): 236–43. doi:10.1002/gene.10158. PMID 12434333. S2CID 7891350.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. PMID 12477932.
Humphray SJ, Oliver K, Hunt AR, et al. (2004). "DNA sequence and analysis of human chromosome 9". Nature. 429 (6990): 369–74. Bibcode:2004Natur.429..369H. doi:10.1038/nature02465. PMC2734081. PMID 15164053.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC528928. PMID 15489334.
Cheng HH, Ying M, Tian YH, et al. (2006). "Transcriptional diversity of DMRT1 (dsx- and mab3-related transcription factor 1) in human testis". Cell Res. 16 (4): 389–93. doi:10.1038/sj.cr.7310050. PMID 16617334.
*1. A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators. (PubMed id 10332030)1, 2, 3, 9 Raymond C.S.... Zarkower D. (1999)
2. Evidence for evolutionary conservation of sex-determining genes. (PubMed id 9490411)1, 2, 3, 9 Raymond C.S....Zarkower D. (1998)
3. Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. (PubMed id 20543847)1, 2, 4 Turnbull C....Rahman N. (2010)
4. Transcriptional diversity of DMRT1 (dsx- and mab3-related transcription factor 1) in human testis. (PubMed id 16617334)1, 2, 9 Cheng H.H....Zhou R.J. (2006)
5. A new submicroscopic deletion that refines the 9p region for sex reversal. (PubMed id 10857744)1, 2, 9 Calvari V.... Guioli S. (2000)
6. A second independent locus within DMRT1 is associated with testicular germ cell tumor susceptibility. (PubMed id 21551455)1, 4 Kanetsky P.A....Nathanson K.L. (2011)
7. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)1, 4 Rose J.E....Uhl G.R. (2010)
8. DNA sequence and analysis of human chromosome 9. (PubMed id 15164053)1, 2 Humphray S.J.... Dunham I. (2004)
9. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1,2 Gerhard D.S....Malek J. (2004)
10. The DM domain protein DMRT1 is a dose-sensitive regul ator of fetal germ cell proliferation and pluripotency. (PubMed id 20007774)1, 9 Krentz A.D....Zarkower D. (2009)
Overview of all the structural information available in the PDB for UniProt: Q9Y5R6 (Doublesex- and mab-3-related transcription factor 1) at the PDBe-KB.
dmrt1, doublesex, related, transcription, factor, also, known, protein, which, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes4yj0identifiersaliases, ct154, dmt1, doublesex, related, transcription, factor, 1external, idso. Doublesex and mab 3 related transcription factor 1 also known as DMRT1 is a protein which in humans is encoded by the DMRT1 gene 5 6 7 DMRT1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes4YJ0IdentifiersAliasesDMRT1 CT154 DMT1 doublesex and mab 3 related transcription factor 1External IDsOMIM 602424 MGI 1354733 HomoloGene 9280 GeneCards DMRT1Gene location Human Chr Chromosome 9 human 1 Band9p24 3Start841 690 bp 1 End969 090 bp 1 Gene location Mouse Chr Chromosome 19 mouse 2 Band19 19 BStart25 482 982 bp 2 End25 581 693 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inplacentathyroid glandleft lobe of thyroid glandhuman musculoskeletal systemmuscular systemmusclelymph nodemusclemuscle of leglower legTop expressed inseminiferous tubuleSertoli cellspermatogoniumspermatidmorulaspermatocyterespiratory epitheliumolfactory epitheliumovaryblastocystMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionDNA binding sequence specific DNA binding RNA polymerase II transcription regulatory region sequence specific DNA binding DNA binding transcription activator activity RNA polymerase II specific chromatin binding metal ion binding protein heterodimerization activity cis regulatory region sequence specific DNA binding DNA binding transcription factor activity protein homodimerization activity identical protein binding DNA binding transcription factor activity RNA polymerase II specificCellular componentcytoplasm nucleusBiological processcell differentiation intracellular signal transduction male gonad development regulation of transcription DNA templated regulation of nodal signaling pathway Sertoli cell differentiation positive regulation of meiosis I negative regulation of transcription by RNA polymerase II transcription by RNA polymerase II male sex determination negative regulation of meiotic nuclear division Sertoli cell development oocyte development transcription DNA templated multicellular organism development developmental process involved in reproduction male germ cell proliferation male sex differentiation cell morphogenesis spermatogenesis positive regulation of mitotic nuclear division positive regulation of male gonad development germ cell migration positive regulation of transcription by RNA polymerase II sex differentiationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez176150796EnsemblENSG00000137090ENSMUSG00000024837UniProtQ9Y5R6Q9QZ59RefSeq mRNA NM 021951NM 001363767NM 015826RefSeq protein NP 068770NP 001350696NP 056641Location UCSC Chr 9 0 84 0 97 MbChr 19 25 48 25 58 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 References 3 Further reading 4 External linksFunction editDMRT1 is a dose sensitive transcription factor protein that regulates Sertoli cells and germ cells The DMRT1 gene is located at the end of the 9th chromosome This gene is found in a cluster with two other members of the gene family having in common a zinc finger like DNA binding motif DM domain The DM domain is an ancient conserved component of the vertebrate sex determining pathway that is also a key regulator of male development in flies and nematodes and is found to be the key sex determining factor in chickens 8 The majority of DMRT1 protein is located in the testicular cord and Sertoli cells with a small amount in the germ cells Defective testicular development and XY feminization occur when this gene is hemizygous 5 Two copies of the DMRT1 gene are required for normal sexual development When a DMRT1 gene is lost the most common disease is chromosome 9p deletion which causes abnormal testicular formation and feminization The DMRT1 gene is critical for male sex determination without this gene the female characteristic takes over and male characteristic is slight or non existent When DMRT1 is knocked out in mice the mice showed changes in both Sertoli and germ cells soon after formation of the gonadal ridge The main defects associated with DMRT1 knockout were developmental arrest excess proliferation of germ cells and failure to undergo meiosis mitosis or migration Thus the knockout model shows that loss of the DMRT1 gene is associated with incomplete germ cell development leading to infertility abnormal testicular formation and or feminization of the affected individual citation needed Induced knockout of DMRT1 in adult male mice has been found to cause transdifferentiation of somatic cells in the testis to the equivalent cell types that would ordinarily be found in the ovary 9 Conversely conditional expression of DMRT1 in the gonad of female mice caused the apparent transdifferentiation of ovarian somatic granulosa cells to the equivalent cell type Sertoli ordinarily found in males 10 References edit a b c GRCh38 Ensembl release 89 ENSG00000137090 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000024837 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b Entrez Gene DMRT1 doublesex and mab 3 related transcription factor 1 Raymond CS Shamu CE Shen MM Seifert KJ Hirsch B Hodgkin J Zarkower D February 1998 Evidence for evolutionary conservation of sex determining genes Nature 391 6668 691 5 Bibcode 1998Natur 391 691R doi 10 1038 35618 PMID 9490411 S2CID 11414843 Raymond CS Parker ED Kettlewell JR Brown LG Page DC Kusz K Jaruzelska J Reinberg Y Flejter WL Bardwell VJ Hirsch B Zarkower D June 1999 A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators Hum Mol Genet 8 6 989 96 doi 10 1093 hmg 8 6 989 PMID 10332030 Smith CA Roeszler KN Ohnesorg T Cummins DM Farlie PG Doran TJ Sinclair AH August 2009 The avian Z linked gene DMRT1 is required for male sex determination in the chicken Nature 461 7261 267 71 Bibcode 2009Natur 461 267S doi 10 1038 nature08298 PMID 19710650 S2CID 4413389 Matson CK Murphy MW Sarver AL Griswold MD Bardwell VJ Zarkower D July 2011 DMRT1 prevents female reprogramming in the postnatal mammalian testis Nature 476 7358 101 4 doi 10 1038 nature10239 PMC 3150961 PMID 21775990 Lindeman RE Gearhart MD Minkina A Krentz AD Bardwell VJ Zarkower D March 2015 Sexual cell fate reprogramming in the ovary by DMRT1 Curr Biol 25 6 764 71 Bibcode 2015CBio 25 764L doi 10 1016 j cub 2015 01 034 PMC 4366330 PMID 25683803 Anthony D Krentza b Mark W Murphya Shinseog Kima 1 Matthew S Cookc Blanche Capelc Rui Zhud Angabin Matind Aaron L Sarvere Keith L Parkerf Michael D Griswoldg Leendert H J Looijengah Vivian J Bardwella and David Zarkower The DM Domain Protein DMRT1 Is a Dose sensitive Regulator of Fetal Germ Cell Proliferation and Pluripotency The DM Domain Protein DMRT1 Is a Dose sensitive Regulator of Fetal Germ Cell Proliferation and Pluripotency PNAS 29 Oct 2009 Web 12 Mar 2014 Christopher S Raymond1 Emily D Parker2 Jae R Kettlewell1 Laura G Brown3 David C Page3 Kamila Kusz4 Jadwiga Jaruzelska4 Yuri Reinberg5 Wendy L Flejter6 Vivian J Bardwell1 2 Betsy Hirsch7 and David Zarkower1 Human Molecular Genetics A Region of Human Chromosome 9p Required for Testis Development Contains Two Genes Related to Known Sexual Regulators Oxford Journal n d Web 28 Feb 2014 Craig A Smith Kelly N Roeszler Thomas Ohnesorg David M Cummins Peter G Farlie Timothy J Doran amp Andrew H Sinclair The Avian Z linked Gene DMRT1 Is Required for Male Sex Determination in the Chicken Nature com Nature 26 Aug 2009 Web 12 Mar 2014 DMRT1 Gene GeneCards Crown Human Genome Center Department of Molecular Genetics the Weizmann Institute of Science http genome ucsc edu 23 Oct 2013 Web 12 Mar 2014 Ning Lei Kaori I Hornbaker Daren A Rice Tatiana Karpova Valentine A Agbor and Leslie L Heckert Sex specific Differences in Mouse DMRT1 Expression Are Both Cell Type and Stage dependent during Gonad Development Sex specific Differences in Mouse DMRT1 Expression Are Both Cell Type and Stage dependent during Gonad Development NIH Public Access 13 June 2007 Web 12 Mar 2014 Further reading editSmith CA McClive PJ Western PS et al 2000 Conservation of a sex determining gene Nature 402 6762 601 2 doi 10 1038 45127 PMID 10604464 S2CID 4401771 Calvari V Bertini V De Grandi A et al 2000 A new submicroscopic deletion that refines the 9p region for sex reversal Genomics 65 3 203 12 doi 10 1006 geno 2000 6160 PMID 10857744 Muroya K Okuyama T Goishi K et al 2000 Sex determining gene s on distal 9p clinical and molecular studies in six cases J Clin Endocrinol Metab 85 9 3094 100 doi 10 1210 jcem 85 9 6771 PMID 10999792 S2CID 22145136 Raymond CS Murphy MW O Sullivan MG et al 2000 Dmrt1 a gene related to worm and fly sexual regulators is required for mammalian testis differentiation Genes Dev 14 20 2587 95 doi 10 1101 gad 834100 PMC 316999 PMID 11040213 Casci T 2001 It s a guy thing Nat Rev Genet 1 3 169 doi 10 1038 35042034 PMID 11252745 S2CID 205010812 Harrington JJ Sherf B Rundlett S et al 2001 Creation of genome wide protein expression libraries using random activation of gene expression Nat Biotechnol 19 5 440 5 doi 10 1038 88107 PMID 11329013 S2CID 25064683 Boyer A Dornan S Daneau I et al 2004 Conservation of the function of DMRT1 regulatory sequences in mammalian sex differentiation Genesis 34 4 236 43 doi 10 1002 gene 10158 PMID 12434333 S2CID 7891350 Strausberg RL Feingold EA Grouse LH et al 2003 Generation and initial analysis of more than 15 000 full length human and mouse cDNA sequences Proc Natl Acad Sci U S A 99 26 16899 903 Bibcode 2002PNAS 9916899M doi 10 1073 pnas 242603899 PMC 139241 PMID 12477932 Humphray SJ Oliver K Hunt AR et al 2004 DNA sequence and analysis of human chromosome 9 Nature 429 6990 369 74 Bibcode 2004Natur 429 369H doi 10 1038 nature02465 PMC 2734081 PMID 15164053 Gerhard DS Wagner L Feingold EA et al 2004 The status quality and expansion of the NIH full length cDNA project the Mammalian Gene Collection MGC Genome Res 14 10B 2121 7 doi 10 1101 gr 2596504 PMC 528928 PMID 15489334 Cheng HH Ying M Tian YH et al 2006 Transcriptional diversity of DMRT1 dsx and mab3 related transcription factor 1 in human testis Cell Res 16 4 389 93 doi 10 1038 sj cr 7310050 PMID 16617334 1 A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators PubMed id 10332030 1 2 3 9 Raymond C S Zarkower D 1999 2 Evidence for evolutionary conservation of sex determining genes PubMed id 9490411 1 2 3 9 Raymond C S Zarkower D 1998 3 Variants near DMRT1 TERT and ATF7IP are associated with testicular germ cell cancer PubMed id 20543847 1 2 4 Turnbull C Rahman N 2010 4 Transcriptional diversity of DMRT1 dsx and mab3 related transcription factor 1 in human testis PubMed id 16617334 1 2 9 Cheng H H Zhou R J 2006 5 A new submicroscopic deletion that refines the 9p region for sex reversal PubMed id 10857744 1 2 9 Calvari V Guioli S 2000 6 A second independent locus within DMRT1 is associated with testicular germ cell tumor susceptibility PubMed id 21551455 1 4 Kanetsky P A Nathanson K L 2011 7 Personalized smoking cessation interactions between nicotine dose dependence and quit success genotype score PubMed id 20379614 1 4 Rose J E Uhl G R 2010 8 DNA sequence and analysis of human chromosome 9 PubMed id 15164053 1 2 Humphray S J Dunham I 2004 9 The status quality and expansion of the NIH full length cDNA project the Mammalian Gene Collection MGC PubMed id 15489334 1 2 Gerhard D S Malek J 2004 10 The DM domain protein DMRT1 is a dose sensitive regul ator of fetal germ cell proliferation and pluripotency PubMed id 20007774 1 9 Krentz A D Zarkower D 2009 External links editDMRT1 protein human at the U S National Library of Medicine Medical Subject Headings MeSH https web archive org web 20110720091853 http www dmrt1 umn edu Overview of all the structural information available in the PDB for UniProt Q9Y5R6 Doublesex and mab 3 related transcription factor 1 at the PDBe KB This article incorporates text from the United States National Library of Medicine which is in the public domain nbsp This article on a gene on human chromosome 9 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title DMRT1 amp oldid 1215986544, wikipedia, wiki, book, books, library,
