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

Claire Eyers; 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 Imhof; Carlos Caldas; Thomas Jenuwein; Manel Esteller

doi:10.1038/ng1531

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

Claire Eyers, 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 AhnAxel Imhof, Carlos Caldas, Thomas Jenuwein, Manel Esteller

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	391-400
Number of pages	9
Journal	Nature Genetics
Volume	37
Issue number	4
DOIs	https://doi.org/10.1038/ng1531
Publication status	Published - Apr 2005

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Eyers, C., Fraga, M. F., Ballestar, E., Villar-Garea, A., Boix-Chornet, M., Espada, J., Schotta, G., Bonaldi, T., Haydon, C., Ropero, S., Petrie, K., Iyer, N. G., Pérez-Rosado, A., Calvo, E., Lopez, J. A., Cano, A., Calasanz, M. J., Colomer, D., Piris, M. Á., ... Esteller, M. (2005). Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nature Genetics, 37(4), 391-400. https://doi.org/10.1038/ng1531

@article{47adc59684ca4e0cb6b624ca00dd07f1,

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.",

author = "Claire Eyers and Fraga, {Mario F.} and Esteban Ballestar and Ana Villar-Garea and Manuel Boix-Chornet and Jesus Espada and Gunnar Schotta and Tiziana Bonaldi and Claire Haydon and Santiago Ropero and Kevin Petrie and Iyer, {N. Gopalakrishna} and Alberto P{\'e}rez-Rosado and Enrique Calvo and Lopez, {Juan A.} and Amparo Cano and Calasanz, {Maria J.} and Dolors Colomer and Piris, {Miguel {\'A}ngel} and Natalie Ahn and Axel Imhof and Carlos Caldas and Thomas Jenuwein and Manel Esteller",

year = "2005",

month = apr,

doi = "10.1038/ng1531",

language = "English",

volume = "37",

pages = "391--400",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "4",

}

Eyers, C, Fraga, MF, Ballestar, E, Villar-Garea, A, Boix-Chornet, M, Espada, J, Schotta, G, Bonaldi, T, Haydon, C, Ropero, S, Petrie, K, Iyer, NG, Pérez-Rosado, A, Calvo, E, Lopez, JA, Cano, A, Calasanz, MJ, Colomer, D, Piris, MÁ, Ahn, N, Imhof, A, Caldas, C, Jenuwein, T & Esteller, M 2005, 'Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer', Nature Genetics, vol. 37, no. 4, pp. 391-400. https://doi.org/10.1038/ng1531

TY - JOUR

T1 - Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer

AU - Eyers, Claire

AU - Fraga, Mario F.

AU - Ballestar, Esteban

AU - Villar-Garea, Ana

AU - Boix-Chornet, Manuel

AU - Espada, Jesus

AU - Schotta, Gunnar

AU - Bonaldi, Tiziana

AU - Haydon, Claire

AU - Ropero, Santiago

AU - Petrie, Kevin

AU - Iyer, N. Gopalakrishna

AU - Pérez-Rosado, Alberto

AU - Calvo, Enrique

AU - Lopez, Juan A.

AU - Cano, Amparo

AU - Calasanz, Maria J.

AU - Colomer, Dolors

AU - Piris, Miguel Ángel

AU - Ahn, Natalie

AU - Imhof, Axel

AU - Caldas, Carlos

AU - Jenuwein, Thomas

AU - Esteller, Manel

PY - 2005/4

Y1 - 2005/4

N2 - 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.

AB - 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.

U2 - 10.1038/ng1531

DO - 10.1038/ng1531

M3 - Article

SN - 1061-4036

VL - 37

SP - 391

EP - 400

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

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

Abstract

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