Nucleic Acids Research, 2002, Vol. 30, No. 17 3831-3838
© 2002 Oxford University Press
Dnmt3L is a transcriptional repressor that recruits histone deacetylase
1 Free University of Brussels, Faculty of Medicine, Laboratory of Molecular Virology, 808 route de Lennik, 1070 Brussels, Belgium, 2 Division of Medical Virology, Faculty of Health Sciences, University of Cape Town Medical School, Anzio Road, Observatory, 7925 Cape Town, South Africa, 3 Wellcome/CRC Institute and Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 1QR, UK and 4 FRE 2527-CNRS, Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue Calmette, 59021 Lille Cedex, France
*To whom correspondence should be addressed. Tel: +32 2 555 62 43; Fax: +32 2 555 62 57; Email: ffuks{at}ulb.ac.be
The Dnmt3L protein belongs to the Dnmt3 family of DNA methyltransferases by virtue of its sequence homology in the plant homeodomain (PHD)-like motif. Dnmt3L is essential for the establishment of maternal genomic imprints and, given its lack of key methyltransferase motifs, is more likely to act as a regulator of methylation rather than as an enzyme that methylates DNA. Here, we show that Dnmt3L, like Dnmt3a and Dnmt3b, interacts both in vitro and in vivo with the histone deacetylase HDAC1. Consistent with the binding to a deacetylase, Dnmt3L purifies histone deacetylase activity from nuclear extracts. We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A. Binding of Dnmt3L to HDAC1 as well as its repressive function require the PHD-like motif. Our results indicate that Dnmt3L plays a role in transcriptional regulation and that recruitment of the HDAC repressive machinery is a shared and conserved feature of the Dnmt3 family. The fact that, despite the absence of a methyltransferase domain, Dnmt3L retains the capacity to contact deacetylase further substantiates the notion that the Dnmts can repress transcription independently of their methylating activities.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. S. Garrison, S. R. Yant, J. G. Mikkelsen, and M. A. Kay Postintegrative Gene Silencing within the Sleeping Beauty Transposition System Mol. Cell. Biol., December 15, 2007; 27(24): 8824 - 8833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bai, K. Ghoshal, and S. T. Jacob Identification of T-cadherin as a Novel Target of DNA Methyltransferase 3B and Its Role in the Suppression of Nerve Growth Factor-mediated Neurite Outgrowth in PC12 Cells J. Biol. Chem., May 12, 2006; 281(19): 13604 - 13611. [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]
|
|
|
|
|
|
G. Gardian, S. E. Browne, D.-K. Choi, P. Klivenyi, J. Gregorio, J. K. Kubilus, H. Ryu, B. Langley, R. R. Ratan, R. J. Ferrante, et al. Neuroprotective Effects of Phenylbutyrate in the N171-82Q Transgenic Mouse Model of Huntington's Disease J. Biol. Chem., January 7, 2005; 280(1): 556 - 563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Vasques, R. Stabellini, F. Xue, X. C. Tian, M. Soukoyan, and L. V. Pereira XIST Repression in the Absence of DNMT1 and DNMT3B DNA Res, January 1, 2005; 12(5): 373 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Suetake, F. Shinozaki, J. Miyagawa, H. Takeshima, and S. Tajima DNMT3L Stimulates the DNA Methylation Activity of Dnmt3a and Dnmt3b through a Direct Interaction J. Biol. Chem., June 25, 2004; 279(26): 27816 - 27823. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-S. Kuan, P. Brewer-Jensen, and L. L. Searles Suppressor of sable, a Putative RNA-Processing Protein, Functions at the Level of Transcription Mol. Cell. Biol., May 1, 2004; 24(9): 3734 - 3746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Fisher, R. Siman-Tov, and S. Ankri Characterization of cytosine methylated regions and 5-cytosine DNA methyltransferase (Ehmeth) in the protozoan parasite Entamoeba histolytica Nucleic Acids Res., January 9, 2004; 32(1): 287 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M D Hodges, H C Rees, M J Seckl, E S Newlands, and R A Fisher Genetic refinement and physical mapping of a biparental complete hydatidiform mole locus on chromosome 19q13.4. J. Med. Genet., August 1, 2003; 40(8): e95 - 95. [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Fahrner and S. B. Baylin Heterochromatin: stable and unstable invasions at home and abroad Genes & Dev., August 1, 2003; 17(15): 1805 - 1812. [Full Text] [PDF]
|
|
|
|
|
|
F. Fuks, P. J. Hurd, R. Deplus, and T. Kouzarides The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase Nucleic Acids Res., May 1, 2003; 31(9): 2305 - 2312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. THIAGALINGAM, K.-H. CHENG, H. J. LEE, N. MINEVA, A. THIAGALINGAM, and J. F. PONTE Histone Deacetylases: Unique Players in Shaping the Epigenetic Histone Code Ann. N.Y. Acad. Sci., March 1, 2003; 983(1): 84 - 100. [Abstract] [Full Text] [PDF]
|
|