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

151 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Espada, J., Ballestar, E., Fraga, M. F., Villar-Garea, A., Juarranz, A., Stockert, J. C., Robertson, K. D., Fuks, F., & 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