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

Heterochromatin marks such as H3K9me3 undergo 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. Here, we investigate the molecular mechanism of H3K9me3 dynamics in medaka (Japanese killifish, Oryzias latipes) as a non-mammalian vertebrate model, and show that rapid cell cycle during cleavage stages causes DNA replication-dependent passive erasure of H3K9me3. We also find 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 demonstrate that cell cycle length in early development also governs H3K9me3 reprogramming in zebrafish and Xenopus laevis. Together with the previous studies in invertebrates, we propose that a cell cycle length-dependent mechanism for both global erasure and re-accumulation of H3K9me3 is conserved among rapid-cleavage species of non-mammalian vertebrates and invertebrates such as Drosophila, C. elegans, Xenopus and teleost fish. Synopsis: H3K9me3 reprogramming dynamics after fertilization are conserved among rapid-cleavage species such as Drosophila, C. elegans, Xenopus, and teleost fish. Data in this study indicate that cell cycle length governs heterochromatin reprogramming during early development in these species. Rapid cell cycle during cleavage stages causes DNA replication-dependent passive erasure of H3K9me3 in medaka. Cell cycle slowing, toward the mid-blastula transition, permits increasing nuclear accumulation of the H3K9me3 histone methyltransferase Setdb1, leading to H3K9me3 re-accumulation in medaka. Cell cycle length in early development also controls H3K9me3 erasure and re-establishment during early development in zebrafish and Xenopus laevis. H3K9me3 reprogramming dynamics after fertilization are conserved among rapid-cleavage species such as Drosophila, C. elegans, Xenopus, and teleost fish. Data in this study indicate that cell cycle length governs heterochromatin reprogramming during early development in these species. [ABSTRACT FROM AUTHOR]