Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer

Mario F. Fraga, Esteban Ballestar, Ana Villar-Garea, Manuel Boix-Chornet, Jesus Espada, Gunnar Schotta, Tiziana Bonaldi, Claire Haydon, Santiago Ropero, Kevin Petrie, N. Gopalakrishna Iyer, Alberto Pérez-Rosado, Enrique Calvo, Juan A. Lopez, Amparo Cano, Maria J. Calasanz, Dolors Colomer, Miguel Ángel Piris, Natalie Ahn, Axel ImhofCarlos Caldas, Thomas Jenuwein, Manel Esteller

Research output: Contribution to journalArticlepeer-review

Abstract

CpG island hypermethylation and global genomic hypomethylation are common epigenetic features of cancer cells. Less attention has been focused on histone modifications in cancer cells. We characterized post-translational modifications to histone H4 in a comprehensive panel of normal tissues, cancer cell lines and primary tumors. Using immunodetection, high-performance capillary electrophoresis and mass spectrometry, we found that cancer cells had a loss of monoacetylated and trimethylated forms of histone H4. These changes appeared early and accumulated during the tumorigenic process, as we showed in a mouse model of multistage skin carcinogenesis. The losses occurred predominantly at the acetylated Lys16 and trimethylated Lys20 residues of histone H4 and were associated with the hypomethylation of DNA repetitive sequences, a well-known characteristic of cancer cells. Our data suggest that the global loss of monoacetylation and trimethylation of histone H4 is a common hallmark of human tumor cells.

Original languageEnglish
Pages (from-to)391-400
Number of pages10
JournalNature Genetics
Volume37
Issue number4
DOIs
Publication statusPublished - Apr 2005

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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