Lsd1 is an essential regulator of the chromatin and transcriptional landscapes during the maternal-to-zygotic

How the parental genomes of the very specialized sperm and oocyte cells are remodelled upon fertilization to confer totipotency has remained a tantalizing open questions. Indeed, in the case of mammals, the parental genomes undergo dramatic reprogramming upon fertilization, including differential dynamics of histone post-translational modifications. The roles of histone modifying enzymes in this process, which are maternally provided, are only just starting to emerge. Here, we explore the function of the oocyte inherited pool of Lsd1/Kdm1a, which encodes a histone H3K4 and K9 demethylase, during early mouse development. Maternal deficiency of Lsd1/Kdm1a results in developmental arrest by the two-cell stage, associated with dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns depending on its demethylase activity. At the transcriptional level, two major changes occur. On one hand, switch from maternal-to-zygotic program fails to be induced. On the other hand, LINE-1 retrotransposons are not properly silenced, along with evidences for increased LINE-1 activity. We propose that Lsd1/Kdm1a is involved in the correct establishment of epigenetic information harboured by histones and is involved in the initiation of new pattern of genome expression driving early mouse development and preserving genome integrity RNA-seq of individual mouse oocytes高度特化的精子与卵母细胞的亲本基因组在受精后如何重塑以赋予细胞全能性（totipotency），长期以来都是一个引人入胜的未解科学问题。具体而言，哺乳动物的亲本基因组在受精后会经历剧烈的重编程过程，其中包含组蛋白翻译后修饰（histone post-translational modifications）的差异化动态变化；而在此过程中发挥功能的母源组蛋白修饰酶（histone modifying enzymes），其具体作用直到近年才刚刚被学界逐步探明。本研究探讨了小鼠早期发育阶段，卵母细胞所继承的、编码组蛋白H3K4与K9去甲基化酶（demethylase）的Lsd1/Kdm1a储备库的功能。研究发现，Lsd1/Kdm1a的母源缺失会导致胚胎发育阻滞于二细胞期（two-cell stage），且该表型与其去甲基化酶活性密切相关，伴随H3K9与H3K4甲基化模式出现剧烈且逐步的异常改变。在转录水平上，存在两类核心异常变化：其一，母源向合子的转录程序转换（maternal-to-zygotic program）无法被正常诱导启动；其二，LINE-1逆转座子（LINE-1 retrotransposons）未能得到有效沉默，同时伴随LINE-1活性上调的相关证据。我们提出，Lsd1/Kdm1a参与了组蛋白所承载的表观遗传信息的正确建立，同时参与调控驱动小鼠早期发育的全新基因组表达模式的启动，并维持基因组完整性。本数据集包含单个小鼠卵母细胞的RNA测序（RNA-seq）数据。