Histone Modifications of Cancer Cells

Considerable effort has been devoted to understanding the relevance of aberrant DNA methylation patterns to human cancer, but much less attention has been focused on histone modifications of cancer cells among many other layers of epigenetic control. Recently, Mario Fraga and colleagues120 characterized the profile of posttranslational modifications of one of the nucleosomal core histones of chromatin, histone H4, in a comprehensive panel of normal tissues, cancer cell lines, and primary tumors. Using immunodetection, high-performance capillary chromatography, and mass spectrometry, Fraga found that cancer cells overall lost monoacetylation at H4-Lys-16 and trimethylation of histone H4-Lys-20.

These are widely regarded as epigenetic markers of malignant transformation, like global hypomethylation and CpG island hypermethylation. In a mouse model of multistage carcinogenesis, these changes appeared early and accumulated during the tumorigenic process. They were also associated with hypomethylation of DNA repetitive sequences, a well-known feature of cancer cells. The data of Fraga et al. suggest that the global loss of monoacetylation and trimethylation of histone 4 might be another common hallmark of human cancer cells.

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