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P008 DNMT3B controls fates in human pluripotent and nullipotent stem cells Patompon Wongtrakoongate and Peter W. Andrews Centre for Stem Cell Biology, Sheffield, United Kingdom DNMT3B is a de novo DNA methyltransferase highly expressed in embryonic stem (ES) and embryonal carcinoma (EC) cells. To determine DNMT3B function in human ES and EC cells, we have established inducible DNMT3B knockdown of human ES cells, and of both human pluripotent and nullipotent EC cells. We find that DNMT3B does not inhibit differentiation and apoptosis in pluripotent ES and EC cells. On the other hand, it facilitates differentiation of human ES cells, and acts as a barrier of induced pluripotency, suggesting its role in closed chromatin state. In contrast to the pluripotent stem cells, DNMT3B is required to prevent apoptosis in the nullipotent EC cells. In addition, Aza-dC treatment induced both differentiation and apoptotic fates of the pluripotent ES and EC cells, though only an apoptotic fate for the nullipotent EC cells. Consistent with earlier studies, these responses are mediated by the presence of DNMT3B, indicating a strong interaction between DNMT3B and chromatin in the stem cells. Similar to DNMT3B knockdown, silencing of OCT4 in nullipotent EC cells, which down-regulated DNMT3B expression, resulted in cells undergoing apoptosis. Moreover, the OCT4 knockdown differentiated cells did not undergo apoptosis induced by Aza-dC. We conclude that DNMT3B is crucial for human pluripotent and nullipotent stem cells to alter their fates, and provide an evidence of the epigenetic drug that targets only cancer stem cell component but not their differentiated counterpart.