Histone macroH2A1 is concentrated in the inactive X chromosome of female preimplantation mouse embryos

MacroH2As are core histone proteins with a hybrid structure consisting of a domain that closely resembles a full-length histone H2A followed by a larg e nonhistone domain. We recently showed that one of the macroH2A subtypes, macroH2A1.2, is concentrated in the inactive X chromosome in adult female m ammals. Here we examine the timing of the association of macroH2A1.2 with t he inactive X chromosome during preimplantation mouse development in order to assess the possibility that macroH2A1 participates in the initiation of X inactivation, The association of macroH2A1.2 with one of the X chromosome s was observed in 50% of blastocysts, occurring mostly, if not exclusively, in extraembryonic cells as was expected from previous studies, which indic ated that X inactivation in embryonic lineages happens after implantation. Examination of earlier embryonic stages indicates that the association of m acroH2A1 with the inactive X chromosome begins between the 8- and 16-cell s tages. Of the changes that are known to happen during X inactivation in pre implantation embryos, the accumulation of macroH2A1 appears to be the earli est marker of the inactive X chromosome and is the only change that has bee n shown to occur during the period when transcriptional silencing is initia ted.