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


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.

DOI: 10.1038/ng1531
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@article{Fraga2005LossOA, title={Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer}, author={Mario Fern{\'a}ndez Fraga and Esteban Ballestar and Ana Villar-Garea and Manuel Boix-Chornet and Jes{\'u}s Espada and Gunnar Schotta and Tiziana Bonaldi and Claire E Haydon and Santiago Ropero and Kevin Petrie and N Gopalakrishna Iyer and Alberto P{\'e}rez-Rosado and Enrique Calvo and Juan A. L{\'o}pez and Amparo Elisabeth Cano and Mar{\'i}a Jos{\'e} Calasanz and Dolors Colomer and Miguel {\'A}ngel Piris and Natalie G Ahn and Axel Imhof and Carlos Caldas and Thomas Jenuwein and Manel Esteller}, journal={Nature Genetics}, year={2005}, volume={37}, pages={391-400} }