In an article entitled, “RNF20 and USP44 Regulate Stem Cell Differentiation by Modulating H2B Monoubiquitylation”, published in June 8, 2012, issue of Molecular Cell 46: 662–673, the lead author Gilad Fuchs with sixteen other associates from nine research groups demonstrated a potential molecular mechanism that connects between cancer and the faulty differentiation of stem cells. This study is a relatively new direction in cancer research. Moreover, the scientists managed to uncover the details of a step in the process of DNA repackaging that takes place during embryonic stem cell differentiation. It turns out that certain pieces of the DNA packaging material must be labeled for the cells to differentiate properly by a molecular tag called ubiquitin. Such tagging is essential for turning on a group of genes, which facilitate the stem cell to differentiate. The researchers identified RNF20 (Ring Finger Protein 20) which enhances the tagging and USP44 (Ubiquitin Specific Protease 44) does the opposite. It appears that both of these switches must function accurately for the differentiation process to proceed efficiently. Furthermore, the study focuses on the role of epigenetics rather than focusing on the genes involved. Understanding the epigenetic roots of cancer will advance the search for effective therapies for this pernicious disease. These experiments might clarify the meaning of molecular defects identified in a number of cancer cases. [summarized by A graduate student, Samsad Razzaque)