Abstract

My laboratory demonstrated that parents transmit not just genetic but also epigenetic information to progeny in the form of histone post-translational modifications. We showed that the H3K27me3 repressive histone mark is retained on post-meiotic oocytes, and it is intergenerationally transmitted from the germline to the next generation. This discovery revealed an entirely unanticipated role for germline- inherited histone modification in mediating gene regulation in the next generation early embryo. We could further show that de novo deposited histone variants and histone acetylation also regulate gene expression in the early embryo, revealing a completely unanticipated role for histone modification-mediated gene regulation at this developmental stage. In the early embryo, the nucleus is also organised de novo in a complex hierarchical folding pattern, including chromatin loops, topologically associating domains (TADs), and compartmental domains. We discovered a novel and fundamental role for HP1a in chromatin reorganisation after fertilisation. We showed that HP1a i) controls the general folding of chromosome arms, ii) controls the clustering and compaction of heterochromatic pericentromeric regions, and iii) contributes to the formation of the B compartment. Our goal is to identify the epigenetic factors that sense environmental changes, bookmark chromatin in the parental germline, and influence on the maternally and paternally inherited epigenomes. Epigenetic inheritance can drive biological diversity. Thus, we expect our discoveries to unveil new concepts of basic biology and evolution.