The histone variant macroH2A is commonly associated with heterochromatin in vertebrates and is usually incorporated after gene silencing has been induced [69]. Interestingly, eggs contain an activity that removes macroH2A from the nucleus after fertilisation and after nuclear transfer [70,71]. The knock-down of macroH2A in MEFs increases the transcriptional reprogramming efficiency of Oct4 and Sox2 in Xenopus oocytes [51]; therefore macroH2A seems to cooperate with other silencing mechanisms to maintain the repressed state of genes in somatic cells and so helps to account for resistance to reprogramming. It is thought that macroH2A may directly restrict reprogramming by preventing transcription factor binding [72], by preventing histone acetylation, and by recruiting Hdacs [73,74]. macroH2A also seems to reduce the affinity of SWI/SNF remodelling complexes for chromatin [75], these complexes being thought to be required for nucleosome mobility and hence for access of factors to repressed genes.
