Mechanisms of Epigenetic Inheritance

A central issue in epigenetics is whether and how epigenetic information in gametes (sperm and egg) is inherited. Cairns and colleagues discovered that "Placeholder" nucleosomes, containing histone variants, occupy DNA regions lacking methylation in both sperm and early embryos. Placeholder nucleosomes establish regions of the genome that lack DNA methylation, and their depletion leads to DNA methylation of promoters and enhancers, and transcriptional silencing. Placeholder nucleosomes reside at promoters of housekeeping genes and early embryonic transcription factors. Housekeeping genes with Placeholder become active when genome-wide transcription is activated, whereas developmental genes with Placeholder become ‘poised' by receiving two additional chromatin modifications, which are targeted by particular transcription factors. Taken together, the results defined a chromatin entity - Placeholder nucleosomes - that are inherited from the germline and remain at promoters and enhancers in embryos, where they help define both active and ‘poised' genes in the embryo.