Abstract:
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.
摘要:
异染色质标记如H3K9me3在受精后经历整体擦除和重建,H3K9me3的正确重新编程对于早期开发至关重要。尽管在无脊椎动物和非哺乳动物脊椎动物中异染色质重编程的动态广泛保守,先前的研究表明,潜在的机制可能在物种之间有所不同。这里,我们研究了medaka中H3K9me3动力学的分子机制(日本killifish,Oryziaslatipes)作为非哺乳动物脊椎动物模型,并表明裂解阶段的快速细胞周期导致H3K9me3的DNA复制依赖性被动擦除。我们还发现细胞周期减慢,朝向囊胚中部过渡,允许增加H3K9me3组蛋白甲基转移酶Settdb1的核积累,导致H3K9me3重新积累。我们进一步证明,早期发育中的细胞周期长度也控制着斑马鱼和非洲爪爪狼的H3K9me3重编程。加上以前在无脊椎动物中的研究,我们认为,在非哺乳动物脊椎动物和无脊椎动物如果蝇的快速裂解物种中,H3K9me3的整体擦除和再积累的细胞周期长度依赖性机制是保守的,C.秀丽隐杆线虫,非洲爪鱼和硬骨鱼。