Heterochromatin Protein 1γ Regulates Epigenetic Reprogramming in Primordial Germ Cells. Mus musculus

Temporal and spatial regulation of trimethylation of histone H3 lysine27 (H3K27me3) is crucial for cell lineage commitment and development. Resetting the ground state of H3K27me3 is important for establishing a proper development program of primordial germ cells (PGCs). The mechanisms that regulate global erasure of epigenetic information in the germ line are not well understood. Here we show that HP1γ suppresses the demethylation activity of Utx through direct interaction in vitro and in vivo. Down-regulation of mammalian heterochromatin protein 1 gamma (HP1γ) coincides with transient loss of H3K27me3 in PGCs on Embryonic Day 10.5 (E10.5). Furthermore, transient abolishment of HP1γ promotes the induction of embryonic stem cells into putative PGCs in vitro. These data reveal a cross-talk between HP1γ and Utx in controlling histone H3K27 methylation status, thereby define HP1γ as a molecular regulator of germ cell epigenetic reprogramming. Overall design: Examination of H3K27me3 modification and HP1γ in HP1γ-depleted mouse ESCs.