Macro Histone Variants Are Critical for the Differentiation of Human Pluripotent Cells

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. Background: Macro histone variant expression is induced during cell differentiation. Results: Human pluripotent cells knocked down for macro histone variants show improper in vitro differentiation. Conclusion: Macro histone variants are critical for the proper silencing of genes during in vitro differentiation. Significance: Proper macro histone deposition is critical for the in vitro generation of good quality differentiated cell types.