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.
Fraga
Mario F
MF
Cancer Epigenetics Laboratory, Molecular Pathology Program, Spanish National Cancer Center, Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Ballestar
Esteban
E
Villar-Garea
Ana
A
Boix-Chornet
Manuel
M
Espada
Jesus
J
Schotta
Gunnar
G
Bonaldi
Tiziana
T
Haydon
Claire
C
Ropero
Santiago
S
Petrie
Kevin
K
Iyer
N Gopalakrishna
NG
Pérez-Rosado
Alberto
A
Calvo
Enrique
E
Lopez
Juan A
JA
Cano
Amparo
A
Calasanz
Maria J
MJ
Colomer
Dolors
D
Piris
Miguel Angel
MA
Ahn
Natalie
N
Imhof
Axel
A
Caldas
Carlos
C
Jenuwein
Thomas
T
Esteller
Manel
M
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
D006657:Histones; D008239:Lysine