USP26 functions as a negative regulator of cellular reprogramming by stabilising PRC1 complex components

Despite much progress in the comprehension of the complex process of somatic cell reprogramming, many questions regarding the molecular mechanism of regulation remain to be answered. At present, the knowledge on the negative regulation of reprogramming process is indeed poor in contrary to the identification of positive regulators. Here we report for the first time that ubiquitin-specific protease 26 negatively regulates somatic cell-reprogramming process by stabilizing chromobox (CBX)-containing proteins CBX4 and CBX6 of polycomb-repressive complex 1 through the removal of K48-linked polyubiquitination. Thus, accumulated CBX4 and CBX6 repress the expression of pluripotency genes, such as Sox2 and Nanog, through PRC1 complexes to ubiquitinate histone H2A at their promoters. In all, our findings have revealed an essential role for ubiquitin-specific protease 26 in cellular reprogramming through polycomb-repressive complex 1.