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Valproic acid (VPA) is a histone deacetylase inhibitor with potent antitumor activity. Valproic acid treatment promotes histone acetylation allowing the chromatin to adopt a relaxed structure facilitating the binding of ectopically expressed transcription factors or downstream secondary factors. Valproic acid was found to significantly enhance reprogramming efficiencies of OSKM-, OSK- and OS-infected fibroblasts, eliminating the need for the oncogenes c-Myc or Klf4. Valproic acid is believed to induce global transcriptional changes, in particular upregulating embryonic stem cell-specific genes while downregulating MEF-specific genes.