Germ line-inherited H3K27me3 restricts enhancer function during maternal-to-zygotic transition

Gametes carry parental genetic material to the next generation. Stress-induced epigenetic changes in the germline can be inherited and profoundly impact offspring development. However, the molecular mechanisms and consequences of transgenerational epigenetic inheritance are poorly understood. Here, we show that Drosophila oocytes transmit the repressive histone mark H3K27me3 to their offspring. Maternal contribution of the histone methyltransferase Enhancer of zeste, the enzymatic component of the Polycomb Repressive Complex 2, is required for active propagation of H3K27me3 during early embryogenesis. Prior to zygotic genome activation, H3K27me3 prevents aberrant accumulation of the active histone mark H3K27ac at regulatory regions and the precocious activation of lineage specific genes. Disruption of germline-inherited Polycomb epigenetic memory causes embryonic lethality that cannot be rescued by late zygotic re-establishment of H3K27me3.