Garvan Institute of Medical Research, Sydney, NSW, Australia.
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
Nat Commun. 2024 Mar 4;15(1):1977. doi: 10.1038/s41467-024-46085-2.
DNA methylation (5mC) is a repressive gene regulatory mark widespread in vertebrate genomes, yet the developmental dynamics in which 5mC patterns are established vary across species. While mammals undergo two rounds of global 5mC erasure, teleosts, for example, exhibit localized maternal-to-paternal 5mC remodeling. Here, we studied 5mC dynamics during the embryonic development of sea lamprey, a jawless vertebrate which occupies a critical phylogenetic position as the sister group of the jawed vertebrates. We employed 5mC quantification in lamprey embryos and tissues, and discovered large-scale maternal-to-paternal epigenome remodeling that affects ~30% of the embryonic genome and is predominantly associated with partially methylated domains. We further demonstrate that sequences eliminated during programmed genome rearrangement (PGR), are hypermethylated in sperm prior to the onset of PGR. Our study thus unveils important insights into the evolutionary origins of vertebrate 5mC reprogramming, and how this process might participate in diverse developmental strategies.
DNA 甲基化（5mC）是一种广泛存在于脊椎动物基因组中的抑制性基因调控标记，但 5mC 模式建立的发育动态在不同物种中有所不同。哺乳动物经历两轮全局 5mC 擦除，而例如，硬骨鱼则表现出局部的母源到父源 5mC 重塑。在这里，我们研究了无颚脊椎动物七鳃鳗胚胎发育过程中的 5mC 动态，七鳃鳗作为有颚脊椎动物的姐妹群，在系统发育中占据着关键位置。我们采用 5mC 在七鳃鳗胚胎和组织中的定量检测，发现了大规模的母源到父源表观基因组重塑，影响了约 30%的胚胎基因组，并且主要与部分甲基化区域相关。我们进一步证明，在程序性基因组重排（PGR）期间消除的序列，在 PGR 开始之前在精子中高度甲基化。因此，我们的研究揭示了脊椎动物 5mC 重编程的进化起源的重要见解，以及这一过程如何参与不同的发育策略。
