Histone modification and nucleosome mapping in human liver cancer cells

The nucleosome is a fundamental unit of chromatin architecture, but it has been under-evaluated during the analysis of histone modification using ChIP-Seq. Thus, we developed a novel approach for defining histone modification at single nucleosome resolution by synergistic analyses of histone modification data from ChIP-Seq and high-resolution nucleosome mapping data from native MNase-Seq using a PCR-free strategy. With this approach, we have generated histone modification data at the single nucleosome resolution in human embryonic stem cells, normal hepatocytes, and liver cancer cells of both genders, and performed quantitative analysis of epigenetic regulation in stem cell differentiation into hepatocytes and neoplastic transformation of liver cancer. Overall design: We developed a novel algorithm to generate histone modification data at the single nucleosome resolution based on both histone modification data from ChIP-Seq and nucleosome mapping data from native MNase-Seq. We compared single nucleosome resolution of histone modification data between human embryonic stem cells and hepatocytes and between human hepatocytes and liver cancer cells for both genders to reveal quantitative epigenomic regulation in cell differentiation and transformation.