Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery
Proper patterns of genome‐wide DNA methylation, mediated by DNA methyltransferases DNMT1, ‐3A and ‐3B, are essential for embryonic development and genomic stability in mammalian cells. The de novo DNA methyltransferase DNMT3B is of particular interest because it is frequently overexpressed in tumor...
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Published in | Nucleic acids research Vol. 32; no. 9; pp. 2716 - 2729 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Oxford University Press
2004
Oxford Publishing Limited (England) |
Subjects | |
Online Access | Get full text |
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Summary: | Proper patterns of genome‐wide DNA methylation, mediated by DNA methyltransferases DNMT1, ‐3A and ‐3B, are essential for embryonic development and genomic stability in mammalian cells. The de novo DNA methyltransferase DNMT3B is of particular interest because it is frequently overexpressed in tumor cells and is mutated in immunodeficiency, centromere instability and facial anomalies (ICF) syndrome. In order to gain a better understanding of DNMT3B, in terms of the targeting of its methylation activity and its role in genome stability, we biochemically purified endogenous DNMT3B from HeLa cells. DNMT3B co‐purifies and interacts, both in vivo and in vitro, with several components of the condensin complex (hCAP‐C, hCAP‐E and hCAP‐G) and KIF4A. Condensin mediates genome‐wide chromosome condensation at the onset of mitosis and is critical for proper segregation of sister chromatids. KIF4A is proposed to be a motor protein carrying DNA as cargo. DNMT3B also interacts with histone deacetylase 1 (HDAC1), the co‐repressor SIN3A and the ATP‐dependent chromatin remodeling enzyme hSNF2H. Further more, DNMT3B co‐localizes with condensin and KIF4A on condensed chromosomes throughout mitosis. These studies therefore reveal the first direct link between the machineries regulating DNA methylation and mitotic chromosome condensation in mammalian cells. |
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Bibliography: | istex:1304FE1692C8078A855F8690842E538DA7619458 To whom correspondence should be addressed at present address: University of Florida, Department of Biochemistry and Molecular Biology, Box 100245, Gainesville, FL 32610, USA. Tel: +1 301 594 9509; Fax: +1 301 496 4951; Email: keithr@ufl.edu Received January 8, 2004; Revised March 26, 2004; Accepted April 15, 2004 ark:/67375/HXZ-ST08FLBB-3 local:gkh589 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0305-1048 1362-4962 1362-4962 |
DOI: | 10.1093/nar/gkh589 |