Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, China.
Cell Cycle. 2020 Sep;19(17):2226-2234. doi: 10.1080/15384101.2020.1806433. Epub 2020 Aug 14.
After fertilization, highly differentiated sperm and oocyte are reprogrammed to totipotent embryo, which subsequently cleavages and develops into an individual through spatial-temporal differentiation. Histone modifications play critical roles to coordinate with other reprogramming events in early stages of embryogenesis. However, most of studies focus on modifications at N-terminus of histones, those at nucleosome core were not well understood. Here, we characterize the three key acetylation events in the histone H3 core, H3K56/K64/K122ac, in early human embryos. The three residues localize at DNA entry-exit position of the nucleosome. Globally, H3K56ac, H3K64ac and H3K122ac were detectable throughout preimplantation stages, with H3K64ac levels being relatively stronger and H3K122ac levels being much weaker. Besides, H3K56ac level had a peak at two-cell stage. Moreover, we found that LINEs also peak at two-cell stage, and H3K56ac was enriched at young LINE-1 in human ESCs, supporting that H3K56ac is an important driving force for young LINE-1 activation in human preimplantation embryos. Our results suggest that acetylation in the nucleosome core of histone H3 is dynamic and various during preimplantation development, and may drive diverse chromatin remodeling events in this developmental window.
受精后,高度分化的精子和卵子被重新编程为全能胚胎,随后通过时空分化分裂并发育成个体。组蛋白修饰在胚胎发生早期与其他重编程事件协同发挥关键作用。然而,大多数研究都集中在组蛋白 N 端的修饰上,对核小体核心的修饰了解甚少。在这里,我们描述了早期人类胚胎中组蛋白 H3 核心的三个关键乙酰化事件,H3K56/K64/K122ac。这三个残基位于核小体的 DNA 进出口位置。总体而言,H3K56ac、H3K64ac 和 H3K122ac 在整个着床前阶段都可检测到,其中 H3K64ac 水平相对较强,H3K122ac 水平较弱。此外,H3K56ac 水平在两细胞期达到峰值。此外,我们发现 LINEs 也在两细胞期达到峰值,并且 H3K56ac 在人类 ESCs 中的年轻 LINE-1 中富集,这表明 H3K56ac 是人类着床前胚胎中年轻 LINE-1 激活的重要驱动力。我们的研究结果表明,组蛋白 H3 核小体核心中的乙酰化在着床前发育过程中是动态和多样化的,并且可能在这个发育窗口中驱动不同的染色质重塑事件。