Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Published Online August 2, 2007
Science DOI: 10.1126/science.1147939

Reports

Submitted on July 17, 2007
Accepted on July 26, 2007

UHRF1 Plays a Role in Maintaining DNA Methylation in Mammalian Cells

Magnolia Bostick 1, Jong Kyong Kim 2, Pierre-Olivier Estève 2, Amander Clark 1, Sriharsa Pradhan 2*, Steven E. Jacobsen 3*

1 Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
2 New England BioLabs, Ipswich, Massachusetts 01938, USA.
3 Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, 90095, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.

* To whom correspondence should be addressed.
Sriharsa Pradhan , E-mail: pradhan{at}neb.com
Steven E. Jacobsen , E-mail: jacobsen{at}ucla.edu

Epigenetic inheritance in mammals relies in part on robust propagation of DNA methylation patterns throughout development. Here we show that the protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1), also known as NP95 in mouse and ICBP90 in human, is required for maintaining DNA methylation. UHRF1 colocalizes with the maintenance DNA methyltransferase protein DNMT1 throughout S phase. UHRF1 appears to tether DNMT1 to chromatin through its direct interaction with DNMT1. Furthermore UHRF1 contains a methyl DNA binding domain, the SRA (SET and RING Associated) domain, which shows strong preferential binding to hemimethylated CG sites, the physiological substrate for DNMT1. These data suggest that UHRF1 may help recruit DNMT1 to hemimethylated DNA to facilitate faithful replication of DNA methylation.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Epigenetic regulation of killer immunoglobulin-like receptor expression in T cells.
G. Li, M. Yu, C. M. Weyand, and J. J. Goronzy (2009)
Blood 114, 3422-3430
   Abstract »    Full Text »    PDF »
Selective Anchoring of DNA Methyltransferases 3A and 3B to Nucleosomes Containing Methylated DNA.
S. Jeong, G. Liang, S. Sharma, J. C. Lin, S. H. Choi, H. Han, C. B. Yoo, G. Egger, A. S. Yang, and P. A. Jones (2009)
Mol. Cell. Biol. 29, 5366-5376
   Abstract »    Full Text »    PDF »
Mammalian cytosine methylation at a glance.
S. K. T. Ooi, A. H. O'Donnell, and T. H. Bestor (2009)
J. Cell Sci. 122, 2787-2791
   Full Text »    PDF »
Intranuclear Degradation of Polyglutamine Aggregates by the Ubiquitin-Proteasome System.
A. Iwata, Y. Nagashima, L. Matsumoto, T. Suzuki, T. Yamanaka, H. Date, K. Deoka, N. Nukina, and S. Tsuji (2009)
J. Biol. Chem. 284, 9796-9803
   Abstract »    Full Text »    PDF »
Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells.
P.-O. Esteve, H. G. Chin, J. Benner, G. R. Feehery, M. Samaranayake, G. A. Horwitz, S. E. Jacobsen, and S. Pradhan (2009)
PNAS 106, 5076-5081
   Abstract »    Full Text »    PDF »
Relics of repeat-induced point mutation direct heterochromatin formation in Neurospora crassa.
Z. A. Lewis, S. Honda, T. K. Khlafallah, J. K. Jeffress, M. Freitag, F. Mohn, D. Schubeler, and E. U. Selker (2009)
Genome Res. 19, 427-437
   Abstract »    Full Text »    PDF »
Epigenetic reprogramming and induced pluripotency.
K. Hochedlinger and K. Plath (2009)
Development 136, 509-523
   Abstract »    Full Text »    PDF »
UHRF1 binds G9a and participates in p21 transcriptional regulation in mammalian cells.
J. K. Kim, P.-O. Esteve, S. E. Jacobsen, and S. Pradhan (2009)
Nucleic Acids Res. 37, 493-505
   Abstract »    Full Text »    PDF »
A SILAC-based DNA protein interaction screen that identifies candidate binding proteins to functional DNA elements.
G. Mittler, F. Butter, and M. Mann (2009)
Genome Res. 19, 284-293
   Abstract »    Full Text »    PDF »
Talk is cheap--cross-talk in establishment, maintenance, and readout of chromatin modifications.
W. Fischle (2008)
Genes & Dev. 22, 3375-3382
   Abstract »    Full Text »    PDF »
Structure and Hemimethylated CpG Binding of the SRA Domain from Human UHRF1.
C. Qian, S. Li, J. Jakoncic, L. Zeng, M. J. Walsh, and M.-M. Zhou (2008)
J. Biol. Chem. 283, 34490-34494
   Abstract »    Full Text »    PDF »
Vezf1 regulates genomic DNA methylation through its effects on expression of DNA methyltransferase Dnmt3b.
H. Gowher, H. Stuhlmann, and G. Felsenfeld (2008)
Genes & Dev. 22, 2075-2084
   Abstract »    Full Text »    PDF »
The PHD Domain of Np95 (mUHRF1) Is Involved in Large-Scale Reorganization of Pericentromeric Heterochromatin.
R. Papait, C. Pistore, U. Grazini, F. Babbio, S. Cogliati, D. Pecoraro, L. Brino, A.-L. Morand, A.-M. Dechampesme, F. Spada, et al. (2008)
Mol. Biol. Cell 19, 3554-3563
   Abstract »    Full Text »    PDF »
Safeguarding parental identity: Dnmt1 maintains imprints during epigenetic reprogramming in early embryogenesis.
M. R. Branco, M. Oda, and W. Reik (2008)
Genes & Dev. 22, 1567-1571
   Abstract »    Full Text »    PDF »
Complex genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice.
K. Kurimoto, Y. Yabuta, Y. Ohinata, M. Shigeta, K. Yamanaka, and M. Saitou (2008)
Genes & Dev. 22, 1617-1635
   Abstract »    Full Text »    PDF »
Histone Deacetylase Inhibitor Depsipeptide Activates Silenced Genes through Decreasing both CpG and H3K9 Methylation on the Promoter.
L.-P. Wu, X. Wang, L. Li, Y. Zhao, S. Lu, Y. Yu, W. Zhou, X. Liu, J. Yang, Z. Zheng, et al. (2008)
Mol. Cell. Biol. 28, 3219-3235
   Abstract »    Full Text »    PDF »
ICBP90, a Novel Methyl K9 H3 Binding Protein Linking Protein Ubiquitination with Heterochromatin Formation.
P. Karagianni, L. Amazit, J. Qin, and J. Wong (2008)
Mol. Cell. Biol. 28, 705-717
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)