HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsumura, A. Articles by Okano, M. Search for Related Content PubMed PubMed Citation Articles by Tsumura, A. Articles by Okano, M.

¹ Laboratory for Mammalian Epigenetic Studies,
² Laboratory for Chromatin Dynamics, and ³ Laboratory for Systems Biology, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan
⁴ Department of Viral Oncology, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8501, Japan
⁵ Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan
⁶ INTEC Web and Genome Informatics Corp., 1-3-3 Shinsuna, Koto-ku, Tokyo 136-8637, Japan
⁷ Epigenetics Program, Novartis Institute for Biomedical Research, 250 Massachusetts Ave., Cambridge, MA 02139, USA

DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b cooperatively regulate cytosine methylation in CpG dinucleotides in mammalian genomes, providing an epigenetic basis for gene silencing and maintenance of genome integrity. Proper CpG methylation is required for the normal growth of various somatic cell types, indicating its essential role in the basic cellular function of mammalian cells. Previous studies using Dnmt1^–/– or Dnmt3a^–/–Dnmt3b^–/– ES cells, however, have shown that undifferentiated embryonic stem (ES) cells can tolerate hypomethylation for their proliferation. In an attempt to investigate the effects of the complete loss of CpG DNA methyltransferase function, we established mouse ES cells lacking all three of these enzymes by gene targeting. Despite the absence of CpG methylation, as demonstrated by genome-wide methylation analysis, these triple knockout (TKO) ES cells grew robustly and maintained their undifferentiated characteristics. TKO ES cells retained pericentromeric heterochromatin domains marked with methylation at Lys9 of histone H3 and heterochromatin protein-1, and maintained their normal chromosome numbers. Our results indicate that ES cells can maintain stem cell properties and chromosomal stability in the absence of CpG methylation and CpG DNA methyltransferases.

^* Correspondence: E-mail: okano{at}cdb.riken.jp

This article has been cited by other articles:

				B.V. Johnson, N. Shindo, P.D. Rathjen, J. Rathjen, and R.A. Keough Understanding pluripotency--how embryonic stem cells keep their options open Mol. Hum. Reprod., September 1, 2008; 14(9): 513 - 520. [Abstract] [Full Text] [PDF]

				R. Papait, C. Pistore, U. Grazini, F. Babbio, S. Cogliati, D. Pecoraro, L. Brino, A.-L. Morand, A.-M. Dechampesme, F. Spada, et al. The PHD Domain of Np95 (mUHRF1) Is Involved in Large-Scale Reorganization of Pericentromeric Heterochromatin Mol. Biol. Cell, August 1, 2008; 19(8): 3554 - 3563. [Abstract] [Full Text] [PDF]

				D. S. Dunican, A. Ruzov, J. A. Hackett, and R. R. Meehan xDnmt1 regulates transcriptional silencing in pre-MBT Xenopus embryos independently of its catalytic function Development, April 1, 2008; 135(7): 1295 - 1302. [Abstract] [Full Text] [PDF]

				S.-i. Takebayashi, T. Tamura, C. Matsuoka, and M. Okano Major and Essential Role for the DNA Methylation Mark in Mouse Embryogenesis and Stable Association of DNMT1 with Newly Replicated Regions Mol. Cell. Biol., December 1, 2007; 27(23): 8243 - 8258. [Abstract] [Full Text] [PDF]

				M. Damelin and T. H. Bestor Biological Functions of DNA Methyltransferase 1 Require Its Methyltransferase Activity Mol. Cell. Biol., June 1, 2007; 27(11): 3891 - 3899. [Abstract] [Full Text] [PDF]

				S. Kobayakawa, K. Miike, M. Nakao, and K. Abe Dynamic changes in the epigenomic state and nuclear organization of differentiating mouse embryonic stem cells Genes Cells, April 1, 2007; 12(4): 447 - 460. [Abstract] [Full Text] [PDF]

				H. Niwa How is pluripotency determined and maintained? Development, February 15, 2007; 134(4): 635 - 646. [Abstract] [Full Text] [PDF]

				M. Oda, A. Yamagiwa, S. Yamamoto, T. Nakayama, A. Tsumura, H. Sasaki, K. Nakao, E. Li, and M. Okano DNA methylation regulates long-range gene silencing of an X-linked homeobox gene cluster in a lineage-specific manner Genes & Dev., December 15, 2006; 20(24): 3382 - 3394. [Abstract] [Full Text] [PDF]