卵母细胞减数分裂
中文名称
通路描述
在减数分裂中，DNA 复制后经历两次染色体分离，分别称为减数 I 和减数 II。在减数 I 中，同源染色体重组并分离至相反极，而姐妹染色单体在减数 II 中分离。在脊椎动物中，未成熟的卵母细胞停滞在减数 I 的前期（PI）。减数分裂的恢复由孕激素刺激，使其通过两个连续的 M 期（MI 和 MII）到达第二个停滞期（MII）。驱动减数分裂进展的关键活动是 MPF（成熟促进因子），它是 CDC2（细胞周期 2 激酶）和 Cyclin B 的异二聚体。在 PI 停滞的卵母细胞中，MPF 初始处于无活性状态，由孕激素诱导的新合成的 Mos 通过双特异性 CDC25C 磷酸酶激活。MPF 的激活介导从 PI 停滞到 MI 的过渡。随后，为了退出 MI 进入间期，MPF 水平必须降低，这一过程由负反馈循环诱导，其中 CDC2 激活 APC（有丝分裂促进复合物），导致 Cyclin B 的破坏。MII 的再激活需要 Cyclin B 的高水平重新积累，以及 APC 由新合成的 Emi2 和其他细胞停滞因子（如 Cyclin E 或高水平的 Mos）的抑制而失活。CSF 通过抑制 APC 的泛素 ligase 活性来阻止 Cyclin B 的破坏，防止在受精前退出减数分裂。受精触发细胞质内游离 Ca2+ 的短暂增加，导致 CSF 失活和 Cyclin B 的破坏，随后卵子从 MII 进入第一个胚胎细胞周期。
英文描述
Replacement of protamines by nucleosomes in the male pronucleus In human sperm, about 85 to 90% of the genome is associated with protamines rather than histones (reviewed in Torres-Flores and Hernández-Hernández 2020, Ribas-Maynou et al. 2022). Protamines provide a much higher packing density of DNA in the nucleus but there are few reports of epigenetic marks on protamines (Brunner et al. 2014). After fertilization, protamines in the male pronucleus are replaced with histones provided by the oocyte cytoplasm (reviewed in Yang et al. 2015, Okada and Yamaguchi 2017). The result is a decondensation of sperm chromatin that produces a chromatin state that is permissive for transcription.
Dissociation of protamines from DNA appears to be controlled by phosphorylation of the protamines PRM1 and PRM2 (inferred from mouse homologs in Gou et al. 2020). The kinase SRPK1 phosphorylates both PRM1 and PRM2, which recruit the histone chaperones Nucleoplasmin 2 (NPM2) and HIRA (inferred from mouse homologs in Gou et al. 2020). NPM2 then dissociates the phosphorylated PRM1 from DNA. By inference NPM1 and NPM3, which are also present in the zygote, may also dissociate PRM1 and PRM2 from DNA (Okuwaki et al. 2012).
Nucleosomes in the zygote are characterized by H3.3 and H2AX (H2A.X) (reviewed in Martire and Banaszynski 2020). HIRA chaperones histone H3.3 and acts together with NPM proteins to assemble nucleosomes from individual histone proteins. Asymmetric dimethylation of H3.3 arginine-17 catalyzed by METTL23 is required for assembly of H3.3 into chromatin in the male pronucleus (inferred from mouse homologs in Hatanaka et al. 2017) . The oocyte-specific histone H1, H1FOO (H1.8, H1-8), is also deposited on the newly formed chromatin at this time and persists until the 8-cell stage (McGraw et al. 2006). In mouse embryos, H1foo is not required for development (Sánchez-Sáez et al. 2022).
Dissociation of protamines from DNA appears to be controlled by phosphorylation of the protamines PRM1 and PRM2 (inferred from mouse homologs in Gou et al. 2020). The kinase SRPK1 phosphorylates both PRM1 and PRM2, which recruit the histone chaperones Nucleoplasmin 2 (NPM2) and HIRA (inferred from mouse homologs in Gou et al. 2020). NPM2 then dissociates the phosphorylated PRM1 from DNA. By inference NPM1 and NPM3, which are also present in the zygote, may also dissociate PRM1 and PRM2 from DNA (Okuwaki et al. 2012).
Nucleosomes in the zygote are characterized by H3.3 and H2AX (H2A.X) (reviewed in Martire and Banaszynski 2020). HIRA chaperones histone H3.3 and acts together with NPM proteins to assemble nucleosomes from individual histone proteins. Asymmetric dimethylation of H3.3 arginine-17 catalyzed by METTL23 is required for assembly of H3.3 into chromatin in the male pronucleus (inferred from mouse homologs in Hatanaka et al. 2017) . The oocyte-specific histone H1, H1FOO (H1.8, H1-8), is also deposited on the newly formed chromatin at this time and persists until the 8-cell stage (McGraw et al. 2006). In mouse embryos, H1foo is not required for development (Sánchez-Sáez et al. 2022).
所含基因
23 个基因