Cell cycle length regulates heterochromatin reprogramming during early development in non-mammalian vertebrates

Abstract

AbstractHeterochromatin marks such as H3K9me3 undergoes global erasure and re-establishment after fertilization, and the proper reprogramming of H3K9me3 is essential for early development. Despite the widely conserved dynamics of heterochromatin reprogramming in invertebrates and non-mammalian vertebrates, previous studies have shown that the underlying mechanisms may differ between species. In this study, we investigated the molecular mechanism of H3K9me3 dynamics in medaka (Japanese killifish,Oryzias latipes) as a non-mammalian vertebrate model, and found that rapid cell cycle during the cleavage stages causes DNA replication-dependent passive erasure of H3K9me3. We also found that cell cycle slowing, toward the mid-blastula transition, permits increasing nuclear accumulation of H3K9me3 histone methyltransferase Setdb1, leading to the onset of H3K9me3 re-accumulation. We further demonstrated that cell cycle length in early development regulates H3K9me3 reprogramming in zebrafish andXenopus laevisas well. Together with the previous studies in invertebrates, we propose that the cell cycle length-dependent mechanism for both global erasure and re-accumulation of H3K9me3 is widely conserved among rapid-cleavage species of non-mammalian vertebrates and invertebrates such asDrosophila,C. elegansand teleost fish.