PMID: 10555141Nov 11, 1999

DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development

Cell
M OkanoEn Li

Abstract

The establishment of DNA methylation patterns requires de novo methylation that occurs predominantly during early development and gametogenesis in mice. Here we demonstrate that two recently identified DNA methyltransferases, Dnmt3a and Dnmt3b, are essential for de novo methylation and for mouse development. Inactivation of both genes by gene targeting blocks de novo methylation in ES cells and early embryos, but it has no effect on maintenance of imprinted methylation patterns. Dnmt3a and Dnmt3b also exhibit nonoverlapping functions in development, with Dnmt3b specifically required for methylation of centromeric minor satellite repeats. Mutations of human DNMT3B are found in ICF syndrome, a developmental defect characterized by hypomethylation of pericentromeric repeats. Our results indicate that both Dnmt3a and Dnmt3b function as de novo methyltransferases that play important roles in normal development and disease.

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Feb 5, 2008·Molekuliarnaia biologiia·E A MoskalevJ D Hoheisel
Jul 1, 2010·Molekuliarnaia biologiia·O V DiachenkoIa I Bur'ianov
Jan 11, 2000·Journal of Medical Genetics·C A Johnson
May 23, 2001·Journal of Medical Genetics·J F Costello, Christoph Plass
Sep 13, 2012·Genome Génome / Conseil National De Recherches Canada·Aabida SaferaliAnna K Naumova
Aug 5, 2003·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Giuseppe ZardoPaola Caiafa
Aug 5, 2003·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Harriet L Harris, Henk R Braig
Jun 17, 2005·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Michèle J Hoffmann, Wolfgang A Schulz
Jun 17, 2005·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Irina Stancheva
Aug 12, 2005·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Zhao-xia Chen, Arthur D Riggs
Aug 29, 2006·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Ana C D'Alessio, Moshe Szyf
Jul 10, 2013·Annual Review of Cell and Developmental Biology·Joan C Ritland PolitzM Groudine
Feb 24, 2005·Annual Review of Plant Biology·Judith Bender
May 3, 2005·Annual Review of Plant Biology·Tzung-Fu Hsieh, Robert L Fischer
Jun 15, 2005·Annual Review of Biochemistry·Mary Grace Goll, Timothy H Bestor
Oct 16, 2004·Annual Review of Genomics and Human Genetics·Yong-Hui JiangArthur L Beaudet
May 18, 2007·Annual Review of Genomics and Human Genetics·Douglas R HiggsRichard Gibbons
Oct 17, 2007·Annual Review of Medicine·Einav Nili Gal-YamPeter A Jones
Apr 27, 2010·Annual Review of Nutrition·Graham C Burdge, Karen A Lillycrop
Jun 11, 2002·Annual Review of Nutrition·I B Van den Veyver
Oct 9, 2008·Annual Review of Pathology·Christine A Iacobuzio-Donahue
Jan 25, 2002·Annual Review of Pharmacology and Toxicology·Jay I Goodman, Rebecca E Watson
Apr 12, 2005·Annual Review of Pharmacology and Toxicology·Manel Esteller
May 8, 2010·Journal of Applied Physiology·Susana Gonzalo
Jan 5, 2011·Journal of Biomedicine & Biotechnology·S J TunsterRosalind M John
Apr 3, 2008·Cancer Research·Linda E KelemenEllen L Goode
May 28, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Katsuhiko NoshoShuji Ogino
Apr 1, 2006·Cytogenetic and Genome Research·R Holmes, P D Soloway
Aug 7, 2010·Circulation Research·Alika K MaunakeaKeji Zhao
May 18, 2011·Circulation·Diane E HandyJoseph Loscalzo
Apr 29, 2010·The Journal of Clinical Investigation·Golo Kronenberg, Matthias Endres
Apr 7, 2010·The Journal of Clinical Investigation·Emin MaltepeSusan J Fisher
Dec 3, 2011·The Journal of Clinical Investigation·Ryan A HladyRene Opavsky
Feb 23, 2000·The Journal of Clinical Investigation·B Tycko
Jun 6, 2009·Journal of Dental Research·S P Barros, S Offenbacher
Mar 1, 2010·Genes & Cancer·Stefano AmatoriMirco Fanelli
Feb 8, 2006·Respiratory Research·Ian M AdcockP J Barnes
Dec 18, 2013·BMC Bioinformatics·Robert Lowe, Vardhman K Rakyan
Oct 21, 2005·BMC Developmental Biology·Tamara H L SmithRoss A McGowan
Sep 19, 2007·BMC Developmental Biology·Sophie La SalleJacquetta M Trasler
Apr 21, 2007·BMC Developmental Biology·Diana LuciferoJacquetta M Trasler
Jan 14, 2009·BMC Genomics·Toshiaki MatsuiTatsuhiko Kadowaki
Aug 9, 2006·Journal of Translational Medicine·Blanca Segura-PachecoAlfonso Duenas-González
Jun 15, 2010·Journal of Translational Medicine·Luca SigalottiMichele Maio
Mar 15, 2008·Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology·Moshe Szyf, Michael J Meaney
May 31, 2011·BMC Biology·Geneviève LavoieYves St-Pierre
Aug 27, 2011·BMC Medicine·Yuanyuan LiTrygve O Tollefsbol
Jun 8, 2013·Particle and Fibre Toxicology·Bram G JanssenTim S Nawrot
May 26, 2006·Orphanet Journal of Rare Diseases·Melanie EhrlichCorry Weemaes
Jun 8, 2011·BMC Proceedings·Masahiro KanedaTakashi Nagai
Jan 21, 2011·Molecular Brain·Nam-Kyung YuBong-Kiun Kaang
Nov 19, 2008·Epigenetics & Chromatin·Tatyana NesterovaNeil Brockdorff
Nov 6, 2009·Epigenetics & Chromatin·Kyoko Hiragami-HamadaRichard Festenstein
Jun 10, 2009·Epigenetics & Chromatin·Cecilia de BustosBarbara J Trask
Sep 28, 2010·Epigenetics & Chromatin·Steen K T OoiTimothy H Bestor
Nov 28, 2013·Epigenetics & Chromatin·Günter RaddatzF Lyko
Nov 3, 2011·Arthritis Research & Therapy·Travis Hughes, Amr H Sawalha
Sep 4, 2003·Genome Biology·Christine Chevalier-MarietteJean-François Nicolas
May 8, 2008·Genome Biology·Eric EspagnePhilippe Silar
Nov 6, 2008·Journal of Biology·Barbara Panning
Mar 22, 2006·Pediatric Research·Hao Wu, Yi Eve Sun
Apr 7, 2007·Pediatric Research·Pål SaetromJohn J Rossi
Apr 7, 2007·Pediatric Research·Jian FengGuoping Fan
Aug 23, 2011·Pediatric Research·Rui DongShan Zheng
Oct 12, 2013·The AAPS Journal·Yuanyuan LiTrygve O Tollefsbol
Jun 13, 2009·Endocrinology·William G NelsonSrinivasan Yegnasubramanian
Dec 6, 2012·Biology Open·Paulina A LatosBrian D Hendrich
Feb 25, 2010·Development·Lei LiJurrien Dean
Apr 30, 2010·Disease Models & Mechanisms·Melissa Conerly, William M Grady
Aug 7, 2009·Journal of Cell Science·Steen K T OoiTimothy H Bestor
Mar 5, 2009·Journal of Cell Science·Stephanie BriersHeidi G Sutherland
Sep 22, 2001·Cell Structure and Function·T Tada, M Tada
Apr 12, 2013·Circulation Journal : Official Journal of the Japanese Circulation Society·Manuel Rosa-GarridoThomas M Vondriska
Jul 26, 2012·Experimental Biology and Medicine·Inna I KrumanSusan E Bergeson
Mar 28, 2008·RNA·Anja M DuursmaReuven Agami
Oct 10, 2009·The Journal of Reproduction and Development·Ken-Ichi YamanakaMasashi Takahashi
Feb 4, 2011·The Journal of Reproduction and Development·Yayoi ObataTomohiro Kono
Jun 15, 2011·The Journal of Reproduction and Development·Takuro HoriiIzuho Hatada
Mar 23, 2011·The Journal of Reproduction and Development·Yayoi Obata
Jun 4, 2011·The Journal of Reproduction and Development·Koichiro NishinoKunio Shiota
Oct 14, 2006·Genes & Genetic Systems·Ryo FujimotoTakeshi Nishio
Nov 8, 2007·Bioscience, Biotechnology, and Biochemistry·Hiroshi Shiba, Seiji Takayama
Jan 28, 2006·PLoS Genetics·Irina A MaksakovaDixie L Mager
Jul 10, 2007·PLoS Genetics·Concetta CuozzoEnrico V Avvedimento
Oct 14, 2010·PLoS Genetics·Jeffrey M GoodMichael W Nachman
Jul 5, 2012·PLoS Genetics·Julia ArandJörn Walter
Sep 13, 2012·PLoS Genetics·Jonathan IpJeffrey R Mann