EpiRIME · Epigenetic Reprogramming, Inheritance and Memory: Dissect epigenetic transitions at fertilisation and early embryogenesis

During gametogenesis, germ cells undergo profound chromatin reorganisation, condensation and transcriptional shutdown. Upon fertilization, gamete chromatin is epigenetically reprogrammed, generating a totipotent zygote that can give rise to all cell types of the adult organism. The maternal factors that reprogram gametes to totipotency are unknown. The current dogma suggests that the parental epigenetic information must be erased in order to establish totipotency. In contrast, we have recently discovered that maternal gametes transmit the epigenetic H3K27me3 histone modification to the next generation (Zenk et al., Science, 2017) adding to increasing evidence suggesting that gametes convey more than just DNA to the offspring. Nevertheless, the underlying mechanisms and the impact of epigenetic inheritance through the gametes are not yet fully resolved. Critically, the mechanisms and impact of (i) paternal gamete reprogramming, (ii) paternal epigenetic inheritance and (iii) de novo establishment of the zygotic epigenome remain essentially unknown. The objective of this proposal is to unravel the fundamental principles underlying these three major epigenetic transitions in vivo in Drosophila.We will achieve our objective via three aims: (i) We will investigate the mechanisms underlying the reprogramming of sperm chromatin at fertilization. Specifically, we will determine the nature and extent of the contributions of two proteins essential for sperm chromatin reprogramming (ii) We will examine the mechanism of histone H3K27me3 inheritance through the paternal germline (iii) We will genetically dissect the de novo establishment of constitutive heterochromatin in the newly formed zygote. Our investigations of these epigenetic transitions are expected to reveal novel insights into the first steps in the formation of life, and to ultimately advance reproductive and regenerative medicine.