Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery

Theresa M. Geiman, Umesh T. Sankpal, Andrea K. Robertson, Yue Chen, Manjari Mazumdar, Jason T. Heale, John A. Schmiesing, Wankee Kim, Kyoko Yokomori, Yingming Zhao, Keith D Robertson

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

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 over-expressed in tumor cells and is mutated in immuno-deficiency, 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. Furthermore, 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.

Original languageEnglish (US)
Pages (from-to)2716-2729
Number of pages14
JournalNucleic Acids Research
Volume32
Issue number9
DOIs
StatePublished - 2004
Externally publishedYes

Fingerprint

Methyltransferases
Chromosomes
Genomic Instability
DNA Methylation
Mitosis
DNA
Histone Deacetylase 1
Genome
Co-Repressor Proteins
Chromatids
Chromatin Assembly and Disassembly
Centromere
HeLa Cells
Methylation
Embryonic Development
Adenosine Triphosphate
Enzymes
condensin complexes
Neoplasms
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery. / Geiman, Theresa M.; Sankpal, Umesh T.; Robertson, Andrea K.; Chen, Yue; Mazumdar, Manjari; Heale, Jason T.; Schmiesing, John A.; Kim, Wankee; Yokomori, Kyoko; Zhao, Yingming; Robertson, Keith D.

In: Nucleic Acids Research, Vol. 32, No. 9, 2004, p. 2716-2729.

Research output: Contribution to journalArticle

Geiman, TM, Sankpal, UT, Robertson, AK, Chen, Y, Mazumdar, M, Heale, JT, Schmiesing, JA, Kim, W, Yokomori, K, Zhao, Y & Robertson, KD 2004, 'Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery', Nucleic Acids Research, vol. 32, no. 9, pp. 2716-2729. https://doi.org/10.1093/nar/gkh589
Geiman, Theresa M. ; Sankpal, Umesh T. ; Robertson, Andrea K. ; Chen, Yue ; Mazumdar, Manjari ; Heale, Jason T. ; Schmiesing, John A. ; Kim, Wankee ; Yokomori, Kyoko ; Zhao, Yingming ; Robertson, Keith D. / Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery. In: Nucleic Acids Research. 2004 ; Vol. 32, No. 9. pp. 2716-2729.
@article{9a77d1eac5fd4a97b89a4e97ab59a926,
title = "Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery",
abstract = "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 over-expressed in tumor cells and is mutated in immuno-deficiency, 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. Furthermore, 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.",
author = "Geiman, {Theresa M.} and Sankpal, {Umesh T.} and Robertson, {Andrea K.} and Yue Chen and Manjari Mazumdar and Heale, {Jason T.} and Schmiesing, {John A.} and Wankee Kim and Kyoko Yokomori and Yingming Zhao and Robertson, {Keith D}",
year = "2004",
doi = "10.1093/nar/gkh589",
language = "English (US)",
volume = "32",
pages = "2716--2729",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery

AU - Geiman, Theresa M.

AU - Sankpal, Umesh T.

AU - Robertson, Andrea K.

AU - Chen, Yue

AU - Mazumdar, Manjari

AU - Heale, Jason T.

AU - Schmiesing, John A.

AU - Kim, Wankee

AU - Yokomori, Kyoko

AU - Zhao, Yingming

AU - Robertson, Keith D

PY - 2004

Y1 - 2004

N2 - 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 over-expressed in tumor cells and is mutated in immuno-deficiency, 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. Furthermore, 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.

AB - 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 over-expressed in tumor cells and is mutated in immuno-deficiency, 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. Furthermore, 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.

UR - http://www.scopus.com/inward/record.url?scp=2542583103&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2542583103&partnerID=8YFLogxK

U2 - 10.1093/nar/gkh589

DO - 10.1093/nar/gkh589

M3 - Article

C2 - 15148359

AN - SCOPUS:2542583103

VL - 32

SP - 2716

EP - 2729

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 9

ER -