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

J. Biol. Chem., Vol. 279, Issue 26, 27816-27823, June 25, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/26/27816    most recent M400181200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Suetake, I. Articles by Tajima, S. Search for Related Content PubMed PubMed Citation Articles by Suetake, I. Articles by Tajima, S. Social Bookmarking                      What's this?

DNMT3L Stimulates the DNA Methylation Activity of Dnmt3a and Dnmt3b through a Direct Interaction^*

Isao Suetake, Fuminori Shinozaki, Junichi Miyagawa, Hideyuki Takeshima, and Shoji Tajima

From the Division of Physiology, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan

In mammals, the resetting of DNA methylation patterns in early embryos and germ cells is crucial for development. Two DNA methyltransferases, Dnmt3a and Dnmt3b, are responsible for the creation of DNA methylation patterns. Dnmt3L, a member of the Dnmt3 family, has been reported to be necessary for maternal methylation imprinting, possibly by interacting with Dnmt3a and/or Dnmt3b (Hata, K., Okano, M., Lei, H., and Li, E. (2002) Development 129, 1983-1993). In the present study, the effect of DNMT3L, a human homologue of Dnmt3L, on the DNA methylation activity of mouse Dnmt3a and Dnmt3b was examined in vitro. DNMT3L enhanced the DNA methylation activity of Dnmt3a and Dnmt3b about 1.5-3-fold in a dose-dependent manner but did not enhance the DNA methylation activity of Dnmt1. Although the extents of stimulation were different, a stimulatory effect on the DNA methylation activity was observed for all of the substrate DNA sequences examined, such as those of the maternally methylated SNRPN and Lit-1 imprinting genes, the paternally methylated H19 imprinting gene, the CpG island of the myoD gene, the 5 S ribosomal RNA gene, an artificial 28-bp DNA, poly(dG-dC)-poly(dG-dC), and poly(dI-dC)-poly(dI-dC). DNMT3L could not bind to DNA but could bind to Dnmt3a and Dnmt3b, indicating that the stimulatory effect of DNMT3L on the DNA methylation activity may not be due to the guiding of Dnmt3a and Dnmt3b to the targeting DNA sequence but may comprise a direct effect on their catalytic activity. The carboxyl-terminal half of DNMT3L was found to be responsible for the enhancement of the enzyme activity.

Received for publication, January 8, 2004 , and in revised form, April 21, 2004.

^* This work was supported by the Promotion of Basic Research Activities for Innovative Biosciences of Japan, a grant-in-aid from the Ministry of Education, Science, Sports, and Culture of Japan, and the National Project on Protein Structural and Functional Analyses. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 81-6-6879-8627; Fax: 81-6-6879-8629; E-mail: tajima{at}protein.osaka-u.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y.-G. Hu, R. Hirasawa, J.-L. Hu, K. Hata, C.-L. Li, Y. Jin, T. Chen, E. Li, M. Rigolet, E. Viegas-Pequignot, et al. Regulation of DNA methylation activity through Dnmt3L promoter methylation by Dnmt3 enzymes in embryonic development Hum. Mol. Genet., September 1, 2008; 17(17): 2654 - 2664. [Abstract] [Full Text] [PDF]

				N. M Zamudio, S. Chong, and M. K O'Bryan Epigenetic regulation in male germ cells Reproduction, August 1, 2008; 136(2): 131 - 146. [Abstract] [Full Text] [PDF]

				Y. Kato, M. Kaneda, K. Hata, K. Kumaki, M. Hisano, Y. Kohara, M. Okano, E. Li, M. Nozaki, and H. Sasaki Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse Hum. Mol. Genet., October 1, 2007; 16(19): 2272 - 2280. [Abstract] [Full Text] [PDF]

				C. B. Schaefer, S. K. T. Ooi, T. H. Bestor, and D. Bourc'his Epigenetic Decisions in Mammalian Germ Cells Science, April 20, 2007; 316(5823): 398 - 399. [Abstract] [Full Text] [PDF]

				T.C. Shovlin, D. Bourc'his, S. La Salle, A. O'Doherty, J.M. Trasler, T.H. Bestor, and C.P. Walsh Sex-specific promoters regulate Dnmt3L expression in mouse germ cells Hum. Reprod., February 1, 2007; 22(2): 457 - 467. [Abstract] [Full Text] [PDF]

				Y.-Q. Li, P.-Z. Zhou, X.-D. Zheng, C. P. Walsh, and G.-L. Xu Association of Dnmt3a and thymine DNA glycosylase links DNA methylation with base-excision repair Nucleic Acids Res., January 28, 2007; 35(2): 390 - 400. [Abstract] [Full Text] [PDF]

				F. Li, M. Papworth, M. Minczuk, C. Rohde, Y. Zhang, S. Ragozin, and A. Jeltsch Chimeric DNA methyltransferases target DNA methylation to specific DNA sequences and repress expression of target genes Nucleic Acids Res., January 12, 2007; 35(1): 100 - 112. [Abstract] [Full Text] [PDF]

				S.-i. Kageyama, H. Liu, N. Kaneko, M. Ooga, M. Nagata, and F. Aoki Alterations in epigenetic modifications during oocyte growth in mice Reproduction, January 1, 2007; 133(1): 85 - 94. [Abstract] [Full Text] [PDF]

				I. Suetake, D. Hayata, and S. Tajima The Amino-Terminus of Mouse DNA Methyltransferase 1 Forms an Independent Domain and Binds to DNA with the Sequence Involving PCNA Binding Motif J. Biochem., December 1, 2006; 140(6): 763 - 776. [Abstract] [Full Text] [PDF]

				K. Nimura, C. Ishida, H. Koriyama, K. Hata, S. Yamanaka, E. Li, K. Ura, and Y. Kaneda Dnmt3a2 targets endogenous Dnmt3L to ES cell chromatin and induces regional DNA methylation. Genes Cells, October 1, 2006; 11(10): 1225 - 1237. [Abstract] [Full Text] [PDF]

				I. Suetake, Y. Morimoto, T. Fuchikami, K. Abe, and S. Tajima Stimulation Effect of Dnmt3L on the DNA Methylation Activity of Dnmt3a2 J. Biochem., October 1, 2006; 140(4): 553 - 559. [Abstract] [Full Text] [PDF]

				M. S. Kareta, Z. M. Botello, J. J. Ennis, C. Chou, and F. Chedin Reconstitution and Mechanism of the Stimulation of de Novo Methylation by Human DNMT3L J. Biol. Chem., September 8, 2006; 281(36): 25893 - 25902. [Abstract] [Full Text] [PDF]

				Z.-H. Xie, Y.-N. Huang, Z.-X. Chen, A. D. Riggs, J.-P. Ding, H. Gowher, A. Jeltsch, H. Sasaki, K. Hata, and G.-L. Xu Mutations in DNA methyltransferase DNMT3B in ICF syndrome affect its regulation by DNMT3L Hum. Mol. Genet., May 1, 2006; 15(9): 1375 - 1385. [Abstract] [Full Text] [PDF]

				I.B. Van den Veyver and T.K. Al-Hussaini Biparental hydatidiform moles: a maternal effect mutation affecting imprinting in the offspring Hum. Reprod. Update, May 1, 2006; 12(3): 233 - 242. [Abstract] [Full Text] [PDF]

				P. Arnaud, K. Hata, M. Kaneda, E. Li, H. Sasaki, R. Feil, and G. Kelsey Stochastic imprinting in the progeny of Dnmt3L-/- females Hum. Mol. Genet., February 15, 2006; 15(4): 589 - 598. [Abstract] [Full Text] [PDF]

				H. Gowher, K. Liebert, A. Hermann, G. Xu, and A. Jeltsch Mechanism of Stimulation of Catalytic Activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L J. Biol. Chem., April 8, 2005; 280(14): 13341 - 13348. [Abstract] [Full Text] [PDF]

				K. E. Webster, M. K. O'Bryan, S. Fletcher, P. E. Crewther, U. Aapola, J. Craig, D. K. Harrison, H. Aung, N. Phutikanit, R. Lyle, et al. Meiotic and epigenetic defects in Dnmt3L-knockout mouse spermatogenesis PNAS, March 15, 2005; 102(11): 4068 - 4073. [Abstract] [Full Text] [PDF]