Histone tails are subject to numerous post-translational modifications that are important for the regulation of chromatin structure and gene expression [54]. Histone deacetylation commonly accompanies gene repression in differentiated cells. Inhibitors of Hdac, including valproic acid (VPA) and trichostatin A (TSA) often promote the success of nuclear reprogramming (Table 1) [55–57]. For example, the frequency of obtaining cloned offspring by nuclear transfer to mammalian eggs is improved up to fivefold by Hdac inhibition [55,56]. Gene reactivation is also enhanced by Hdac inhibition in induced pluripotency experiments [57]. The downregulation of Hdac2 allows the induction of pluripotency from MEFs solely by expression of miR302/367 [58]. It may be that an inhibition of differentiation programs, together with appropriate culture conditions, may be sufficient for the induction of pluripotency. In Caenorhabditis elegans, expression of the gustatory neurons inducing transcription factor CHE-1 together with either Hdac inhibition or the deletion of the histone chaperone lin-53 allows reprogramming of germ cells into neurons [59]. No other cell type is affected by CHE-1 overexpression, an indication that, in C. elegans, certain chromatin factors can provide a cell type-specific resistance to reprogramming [59]. Altogether, inhibiting Hdac activity generally improves reprogramming.
