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oai:repisalud.isciii.es:20.500.12105/272212026-02-12T01:18:49Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Fraga, Mario F author Ballestar, Esteban author Villar-Garea, Ana author Boix-Chornet, Manuel author Espada, Jesus author Schotta, Gunnar author Bonaldi, Tiziana author Haydon, Claire author Ropero, Santiago author Petrie, Kevin author Iyer, N Gopalakrishna author Pérez-Rosado, Alberto author Calvo, Enrique author Lopez, Juan A author Cano, Amparo author Calasanz, Maria J author Colomer, Dolors author Piris, Miguel Angel author Ahn, Natalie author Imhof, Axel author Caldas, Carlos author Jenuwein, Thomas author Esteller, Manel author 2005-04 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. Nat Genet. 2005 Apr;37(4):391-400. Nature Genetics 15765097 https://hdl.handle.net/20.500.12105/27221 Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer.