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Chunk #14 — Epigenetic barriers to nuclear reprogramming — Chromatin decondensation

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Epigenetic factors influencing resistance to nuclear reprogramming.
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Two components of eggs and oocytes that seem particularly important for chromatin decondensation are nucleoplasmin (a chaperone of histones H2A and H2B) [33], and a special oocyte-specific linker histone named B4 for amphibians or H1foo for mammals [34,35]. B4 incorporation into nuclei transplanted to Xenopus oocytes is complete in few hours, and is necessary for pluripotency gene activation [30]. We interpret these results as indicating an opening of chromatin structure to expose those genes that are quiescent in somatic cells to the transcriptional-activating components of eggs and oocytes. In the case of eggs and oocytes, the opening up of chromosome structure after nuclear transfer may well be global; that is, not gene specific. Supporting this view is the fact that a wide range of genes, including lineage-specific genes normally expressed in muscle, nerve, and so on, start to be transcribed in somatic nuclei transplanted to Xenopus oocytes [36]. Although reprogramming to induced pluripotency may be mechanistically different, the chromatin remodelling enzyme Chd1 has been shown to be important for the induction and maintenance of pluripotency by promoting an open chromatin