The importance of epigenetic mechanisms is most clearly illustrated during early 
development when a totipotent cell goes through multiple cell fate transitions 
to form the many different cell types and tissues that constitute the embryo and 
the adult. The exchange of a canonical H2A histone for the 'repressive' macroH2A 
variant is one of the most striking epigenetic chromatin alterations that can 
occur at the level of the nucleosome. Here, we discuss recent data on macroH2A 
in zebrafish and mouse embryos, in embryonic and adult stem cells and also in 
nuclear reprogramming. We highlight the role of macroH2A in the establishment 
and maintenance of differentiated states and we discuss its still poorly 
recognized function in transcriptional activation.