DNA methylation is dispensable for the growth and survival of the extraembryonic lineages

Current Biology : CB
Morito SakaueMasaki Okano

Abstract

DNA methylation regulates development and many epigenetic processes in mammals, and it is required for somatic cell growth and survival. In contrast, embryonic stem (ES) cells can self-renew without DNA methylation. It remains unclear whether any lineage-committed cells can survive without DNA-methylation machineries. Unlike in somatic cells, DNA methylation is dispensable for imprinting and X-inactivation in the extraembryonic lineages. In ES cells, DNA methylation prevents differentiation into the trophectodermal fate. Here, we created triple-knockout (TKO) mouse embryos deficient for the active DNA methyltransferases Dnmt1, Dnmt3a, and Dnmt3b (TKO) by nuclear transfer (NT), and we examined their development. In chimeric TKO-NT and WT embryos, few TKO cells were found in the embryo proper, but they contributed to extraembryonic tissues. TKO ES cells showed increasing cell death during their differentiation into epiblast lineages, but not during differentiation into extraembryonic lineages. Furthermore, we successfully established trophoblastic stem cells (ntTS cells) from TKO-NT blastocysts. These TKO ntTS cells could self-renew, and they retained the fundamental gene expression patterns of stem cells. Our findings indicated ...Continue Reading

References

Jun 20, 1998·Molecular and Cellular Biology·T CasparyS M Tilghman
Aug 2, 2001·Nature Genetics·J WangT Magnuson
Jun 15, 2006·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Yojiro YamanakaJanet Rossant
Jul 11, 2006·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Akiko TsumuraMasaki Okano
Dec 5, 2006·Stem Cell Reviews·Josephine White, Stephen Dalton
Feb 28, 2007·Nature Genetics·Kevin D Brown, Keith D Robertson
Oct 7, 2008·Nature Cell Biology·Ray Kit NgMyriam Hemberger
Feb 21, 2009·Biology of Reproduction·Seiji TakashimaTakashi Shinohara
Jul 16, 2009·Nature Reviews. Molecular Cell Biology·Myriam HembergerWolf Reik
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Mayumi OdaKunio Shiota
Oct 6, 2009·Nature Genetics·Ann-Marie BröskeFrank Rosenbauer
Jan 19, 2010·Nature·George L SenPaul A Khavari

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Citations

Mar 20, 2012·Chromosoma·Martin Leeb, Anton Wutz
Jul 18, 2012·Proceedings of the National Academy of Sciences of the United States of America·Joshua D TompkinsArthur D Riggs
Oct 16, 2013·The Journal of Cell Biology·Christian ElabdMichael J Conboy
Dec 6, 2012·Biology Open·Paulina A LatosBrian Hendrich
Sep 6, 2014·Reproduction : the Official Journal of the Society for the Study of Fertility·Jason G Knott, Soumen Paul
Jan 27, 2016·Developmental Cell·Miguel R BrancoWolf Reik
Nov 7, 2015·Cellular and Molecular Life Sciences : CMLS·Julie Prudhomme, Céline Morey
Nov 13, 2014·Proceedings of the National Academy of Sciences of the United States of America·Yasuhiro UmemuraKazuhiro Yagita
May 15, 2012·Reproductive Biomedicine Online·Peter J Rugg-Gunn
Apr 19, 2011·Reproductive Biomedicine Online·Claire E Senner
Mar 13, 2014·Current Opinion in Genetics & Development·Tuncay Baubec, Dirk Schübeler
Mar 20, 2013·Seminars in Hematology·Keqin Kathy LiSai-Juan Chen
Jun 3, 2015·Reproduction : the Official Journal of the Society for the Study of Fertility·Chelsea MarchoJesse Mager
Mar 7, 2014·Developmental Biology·Elizabeth H FinnJulie C Baker
Mar 8, 2012·Epigenetics : Official Journal of the DNA Methylation Society·Momo O NakanishiSatoshi Tanaka
Apr 17, 2014·Developmental Cell·Meelad M DawlatyRudolf Jaenisch
Sep 10, 2014·Cellular and Molecular Life Sciences : CMLS·Susannah Varmuza, Kamelia Miri
Jun 27, 2017·Current Opinion in Genetics & Development·Ozren Bogdanović, Ryan Lister
Aug 18, 2017·Reproduction : the Official Journal of the Society for the Study of Fertility·Verónica M Negrón-PérezPeter J Hansen
Jun 21, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Vitor Braga RissiVilceu Bordignon
Jun 7, 2019·Genes & Development·Katrin M SchüleChristof Niehrs
Dec 4, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Baohua ZhangJay M Baltz
Sep 20, 2019·Nature Reviews. Genetics·Myriam HembergerWendy Dean
Aug 23, 2017·Proceedings of the National Academy of Sciences of the United States of America·Yasuhiro UmemuraKazuhiro Yagita
Dec 9, 2020·Molecular Cell·Can SönmezerArnaud Regis Krebs

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