Human DNA methyltransferase 1 is required for maintenance of the histone H3 modification pattern

Jesus Espada, Esteban Ballestar, Mario F. Fraga, Ana Villar-Garea, Angeles Juarranz, Juan C. Stockert, Keith D Robertson, François Fuks, Manel Esteller

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

DNA methyltransferase 1 (DNMT1) plays an essential role in murine development and is thought to be the enzyme primarily responsible for maintenance of the global methylation status of genomic DNA. However, loss of DNMT1 in human cancer cells affects only the methylation status of a limited number of pericentromeric sequences. Here we show that human cancer cells lacking DNMT1 display at least two important differences with respect to wild type cells: a profound disorganization of nuclear architecture, and an altered pattern of histone H3 modification that results in an increase in the acetylation and a decrease in the dimethylation and trimethylation of lysine 9. Additionally, this phenotype is associated with a loss of interaction of histone deacetylases (HDACs) and HP1 (heterochromatin protein 1) with histone H3 and pericentromeric repetitive sequences (satellite 2). Our data indicate that DNMT1 activity, via maintenance of the appropriate histone H3 modifications, contributes to the preservation of the correct organization of large heterochromatic regions.

Original languageEnglish (US)
Pages (from-to)37175-37184
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number35
DOIs
StatePublished - Aug 27 2004
Externally publishedYes

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Histone Code
Methyltransferases
Histones
Maintenance
DNA
Methylation
Cells
Acetylation
Histone Deacetylases
Nucleic Acid Repetitive Sequences
Lysine
Neoplasms
Display devices
Satellites
Phenotype
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Espada, J., Ballestar, E., Fraga, M. F., Villar-Garea, A., Juarranz, A., Stockert, J. C., ... Esteller, M. (2004). Human DNA methyltransferase 1 is required for maintenance of the histone H3 modification pattern. Journal of Biological Chemistry, 279(35), 37175-37184. https://doi.org/10.1074/jbc.M404842200

Human DNA methyltransferase 1 is required for maintenance of the histone H3 modification pattern. / Espada, Jesus; Ballestar, Esteban; Fraga, Mario F.; Villar-Garea, Ana; Juarranz, Angeles; Stockert, Juan C.; Robertson, Keith D; Fuks, François; Esteller, Manel.

In: Journal of Biological Chemistry, Vol. 279, No. 35, 27.08.2004, p. 37175-37184.

Research output: Contribution to journalArticle

Espada, J, Ballestar, E, Fraga, MF, Villar-Garea, A, Juarranz, A, Stockert, JC, Robertson, KD, Fuks, F & Esteller, M 2004, 'Human DNA methyltransferase 1 is required for maintenance of the histone H3 modification pattern', Journal of Biological Chemistry, vol. 279, no. 35, pp. 37175-37184. https://doi.org/10.1074/jbc.M404842200
Espada J, Ballestar E, Fraga MF, Villar-Garea A, Juarranz A, Stockert JC et al. Human DNA methyltransferase 1 is required for maintenance of the histone H3 modification pattern. Journal of Biological Chemistry. 2004 Aug 27;279(35):37175-37184. https://doi.org/10.1074/jbc.M404842200
Espada, Jesus ; Ballestar, Esteban ; Fraga, Mario F. ; Villar-Garea, Ana ; Juarranz, Angeles ; Stockert, Juan C. ; Robertson, Keith D ; Fuks, François ; Esteller, Manel. / Human DNA methyltransferase 1 is required for maintenance of the histone H3 modification pattern. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 35. pp. 37175-37184.
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