Department of Biology, Emory University, 1510 Clifton Rd. NE, Atlanta, GA 30322, USA.
Yerkes National Primate Research Center, 954 Gatewood Rd. NE, Atlanta, GA 39329, USA; Department of Human Genetics, Emory University School of Medicine, 615 Michael St., Atlanta, GA 30322, USA.
Mol Cell. 2019 Jul 11;75(1):154-171.e5. doi: 10.1016/j.molcel.2019.04.014. Epub 2019 May 2.
The epigenetic information present in mammalian gametes and whether it is transmitted to the progeny are relatively unknown. We find that many promoters in mouse sperm are occupied by RNA polymerase II (Pol II) and Mediator. The same promoters are accessible in GV and MII oocytes and preimplantation embryos. Sperm distal ATAC-seq sites containing motifs for various transcription factors are conserved in monkeys and humans. ChIP-seq analyses confirm that Foxa1, ERα, and AR occupy distal enhancers in sperm. Accessible sperm enhancers containing H3.3 and H2A.Z are also accessible in oocytes and preimplantation embryos. Furthermore, their interactions with promoters in the gametes persist during early development. Sperm- or oocyte-specific interactions mediated by CTCF and cohesin are only present in the paternal or maternal chromosomes, respectively, in the zygote and 2-cell stages. These interactions converge in both chromosomes by the 8-cell stage. Thus, mammalian gametes contain complex patterns of 3D interactions that can be transmitted to the zygote after fertilization.
哺乳动物配子中的表观遗传信息及其是否传递给后代相对未知。我们发现，许多小鼠精子中的启动子被 RNA 聚合酶 II（Pol II）和中介体占据。相同的启动子在 GV 和 MII 卵母细胞和着床前胚胎中是可及的。含有各种转录因子基序的精子远端 ATAC-seq 位点在猴子和人类中是保守的。ChIP-seq 分析证实 Foxa1、ERα 和 AR 占据精子中的远端增强子。含有 H3.3 和 H2A.Z 的可及精子增强子在卵母细胞和着床前胚胎中也是可及的。此外，它们与配子中启动子的相互作用在早期发育过程中持续存在。由 CTCF 和 cohesin 介导的精子或卵母细胞特异性相互作用仅存在于合子和 2 细胞阶段的父本或母本染色体中。这些相互作用在 8 细胞阶段在两条染色体上汇聚。因此，哺乳动物配子中含有复杂的 3D 相互作用模式，这些模式可以在受精后传递给合子。
