Laboratoire de Biologie et de Modélisation de la Cellule, CNRS UMR5239, Ecole Normale Supérieure de Lyon, University of Lyon, France.
Laboratoire de Biométrie et Biologie Evolutive, Université Lyon 1, CNRS, UMR 5558, Villeurbanne F-69622, France.
PLoS Genet. 2020 Mar 5;16(3):e1008543. doi: 10.1371/journal.pgen.1008543. eCollection 2020 Mar.
Following fertilization of a mature oocyte, the formation of a diploid zygote involves a series of coordinated cellular events that ends with the first embryonic mitosis. In animals, this complex developmental transition is almost entirely controlled by maternal gene products. How such a crucial transcriptional program is established during oogenesis remains poorly understood. Here, we have performed an shRNA-based genetic screen in Drosophila to identify genes required to form a diploid zygote. We found that the Lid/KDM5 histone demethylase and its partner, the Sin3A-HDAC1 deacetylase complex, are necessary for sperm nuclear decompaction and karyogamy. Surprisingly, transcriptomic analyses revealed that these histone modifiers are required for the massive transcriptional activation of deadhead (dhd), which encodes a maternal thioredoxin involved in sperm chromatin remodeling. Unexpectedly, while lid knock-down tends to slightly favor the accumulation of its target, H3K4me3, on the genome, this mark was lost at the dhd locus. We propose that Lid/KDM5 and Sin3A cooperate to establish a local chromatin environment facilitating the unusually high expression of dhd, a key effector of the oocyte-to-zygote transition.
在成熟卵子受精后，二倍体合子的形成涉及一系列协调的细胞事件，最终导致第一次胚胎有丝分裂。在动物中，这种复杂的发育转变几乎完全由母源基因产物控制。然而，卵子发生过程中如何建立这样一个关键的转录程序仍知之甚少。在这里，我们在果蝇中进行了基于 shRNA 的遗传筛选，以鉴定形成二倍体合子所需的基因。我们发现 Lid/KDM5 组蛋白去甲基酶及其伴侣 Sin3A-HDAC1 去乙酰化酶复合物对于精子核解压缩和核融合是必需的。令人惊讶的是，转录组分析表明，这些组蛋白修饰因子对于 deadhead（dhd）的大量转录激活是必需的，dhd 编码一种母体硫氧还蛋白，参与精子染色质重塑。出乎意料的是，虽然 lid 的敲低往往略微有利于其靶标 H3K4me3 在基因组上的积累，但这种标记在 dhd 基因座上丢失了。我们提出，Lid/KDM5 和 Sin3A 合作建立一个局部染色质环境，有利于 dhd 的异常高表达，dhd 是卵母细胞到合子转变的关键效应因子。
