We have previously shown that macro histone variants (macroH2A) are expressed at 
low levels in stem cells and are up-regulated during differentiation. Here we 
show that the knockdown of macro histone variants impaired the in vitro and in 
vivo differentiation of human pluripotent cells, likely through defects in the 
silencing of pluripotency-related genes. ChIP experiments showed that during 
differentiation macro histone variants are recruited to the regulatory regions 
of pluripotency and developmental genes marked with H3K27me3 contributing to the 
silencing of these genes.