Abstract. In recent years, it has become increasingly clear that abnormal epigenetic modifications, such as DNA methylation and histone modifications are hallmarks of many types of diseases, such as lung cancers and neurodegenerative diseases. Understanding how different epigenetic patterns regulate gene activity and enabling sensitive detection of epigenetic patterns hold the key to developing the next generation of therapeutic and diagnostic tools of human diseases. By combining state-of-the-art quantitative fluorescence spectroscopy with engineering principles, we have established quantitative correlations among epigenetic content, chromosome structure, and gene activity. Such correlations can be used for screening early-stage disease biomarkers and identifying potential epigenetic modifications as novel drug targets. In addition, we have developed protein probes to identify and recognize disease-related DNA methylation marks. Our detection platform offers a simple and cheap DNA methylation detection approach, promising for detecting early stage cancers.