title: Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer.
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.
authors.affiliation: Cancer Epigenetics Laboratory, Molecular Pathology Program, Spanish National Cancer Center, Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors.forename: Mario F
authors.initials: MF
authors.lastname: Fraga
authors.forename: Esteban
authors.initials: E
authors.lastname: Ballestar
authors.forename: Ana
authors.initials: A
authors.lastname: Villar-Garea
authors.forename: Manuel
authors.initials: M
authors.lastname: Boix-Chornet
authors.forename: Jesus
authors.initials: J
authors.lastname: Espada
authors.forename: Gunnar
authors.initials: G
authors.lastname: Schotta
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bonaldi
authors.forename: Claire
authors.initials: C
authors.lastname: Haydon
authors.forename: Santiago
authors.initials: S
authors.lastname: Ropero
authors.forename: Kevin
authors.initials: K
authors.lastname: Petrie
authors.forename: N Gopalakrishna
authors.initials: NG
authors.lastname: Iyer
authors.forename: Alberto
authors.initials: A
authors.lastname: Pérez-Rosado
authors.forename: Enrique
authors.initials: E
authors.lastname: Calvo
authors.forename: Juan A
authors.initials: JA
authors.lastname: Lopez
authors.forename: Amparo
authors.initials: A
authors.lastname: Cano
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Piris
authors.forename: Natalie
authors.initials: N
authors.lastname: Ahn
authors.forename: Axel
authors.initials: A
authors.lastname: Imhof
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
authors.forename: Thomas
authors.initials: T
authors.lastname: Jenuwein
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D000107:Acetylation; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing / Q000502:physiology; D006657:Histones / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008239:Lysine / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D012091:Repetitive Sequences, Nucleic Acid; D014407:Tumor Cells, Cultured
chemical_list: D006657:Histones; D008239:Lysine