Comprehensive Histone Epigenetics (CHEpi): A mass spectrometry based screening assay to measure epigenetic toxicity

Epigenetics have taken center stage in the study of diseases such as cancer, diabetes, and neurodegeneration. For nearly thirty years, it has been known that cancer cells exhibit abnormal DNA methylation patterns. In contrast, the large scale analysis of histone posttranslational modifications (hPTMs) has lagged behind because classically, histone modification analysis has relied on site specific antibody-based techniques. Mass spectrometry (MS) is a technique that holds the promise to picture the histone code comprehensively in a single experiment. Therefore, we developed an MS-based method that is capable of tracking all possible hPTMs in an untargeted approach. In this way, trends in single and combinatorial hPTMs can be reported and enable prediction of the epigenetic toxicity of compounds. Moreover, this method is based on the use of human embryonic stem cells (hESCs), thereby omitting the need to sacrifice laboratory animals. Improving the workflow and the user-friendliness of the assay is an ongoing effort. Still, this novel toxicoepigenetic assay and the data it generates holds great potential for, among others, pharmaceutical industry, food science, clinical diagnostics and, environmental toxicity screening.