Mammalian sperm exhibit epigenetic priming of embryonic and adult regulatory landscapes (ATAC-Seq)

The mammalian sperm genome is generally thought to be condensed and transcriptionally inert. Here we show that most promoters in mouse sperm contain elongating RNA polymerase II and are flanked by several positioned nucleosomes marked by a variety of active histone modifications. The sperm genome is bound by several transcription factors, including Nanog, Oct4, Mediator, condensin, and the pioneer factor FoxA1. These proteins are found at promoters, enhancers, and super-enhancers, many of which are active in mESCs or adult tissues. CTCF and cohesin are also present in sperm DNA, where they mediate interactions that organize the sperm genome into domains and compartments that overlap extensively with those found in mESCs. These results indicate that the sperm genome is rich in epigenetic information and primed for its expression during embryonic and adult life, and suggest mechanisms by which environmental effects on the paternal germline can be transmitted trans-generationally. Overall design: Analysis of the distribution of histone modifications and chromatin proteins in mouse sperm

长期以来，学界普遍认为哺乳动物精子基因组处于高度浓缩状态，且转录活性完全缺失。本研究证实，小鼠精子中的绝大多数启动子区域均结合有处于延伸状态的RNA聚合酶II（RNA polymerase II），其两侧环绕着多个定位精准的核小体，这些核小体带有多种活性组蛋白修饰标记。精子基因组还结合有多种转录因子，包括Nanog、Oct4、Mediator复合物、凝缩蛋白（condensin）以及先驱转录因子FoxA1。这些转录因子富集于启动子、增强子以及超级增强子区域，其中多数区域在小鼠胚胎干细胞（mouse embryonic stem cells, mESCs）或成体组织中具有转录活性。CTCF与黏连蛋白（cohesin）同样存在于精子DNA中，它们介导染色质相互作用，将精子基因组组装为结构域与区室，这些结构与小鼠胚胎干细胞（mESCs）中的染色质结构域和区室高度重合。上述研究结果表明，精子基因组蕴含丰富的表观遗传信息，且已做好在胚胎发育及成体阶段启动基因表达的准备；同时本研究也揭示了父系生殖细胞所受环境影响可跨代传递的潜在分子机制。实验整体设计：分析小鼠精子中组蛋白修饰与染色质蛋白的分布特征。