Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation
Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation
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DOI：
10.7554/elife.08851
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发表时间：
2016-02-02
期刊：
影响因子：
7.7
通讯作者：
Heard, Edith
中科院分区：
文献类型：
--
作者：
Ancelin, Katia;Syx, Laurene;Heard, Edith
受精后，高度特化的精子和卵母细胞基因组被重塑以赋予全能性。发生的戏剧性重编程事件的机制仍然未知，组蛋白修饰酶的假定作用刚刚开始阐明。在这里，我们探讨的功能，卵母细胞遗传池的组蛋白H3 K4和K9去甲基化酶，LSD 1/KDM 1A在早期小鼠发育。KDM 1A缺陷导致发育停滞到两细胞阶段，伴随着H3 K9和H3 K4甲基化模式的显著和逐步改变。在转录水平上，母源到合子转换的开关不能被正确地诱导，LINE-1反转录转座子不能被正确地沉默。我们认为KDM 1A在受精后建立受精卵的正确表观遗传景观，保持基因组完整性和启动驱动早期小鼠发育的基因组表达新模式方面起着关键作用。
Upon fertilization, the highly specialised sperm and oocyte genomes are remodelled to confer totipotency. The mechanisms of the dramatic reprogramming events that occur have remained unknown, and presumed roles of histone modifying enzymes are just starting to be elucidated. Here, we explore the function of the oocyte-inherited pool of a histone H3K4 and K9 demethylase, LSD1/KDM1A during early mouse development. KDM1A deficiency results in developmental arrest by the two-cell stage, accompanied by dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns. At the transcriptional level, the switch of the maternal-to-zygotic transition fails to be induced properly and LINE-1 retrotransposons are not properly silenced. We propose that KDM1A plays critical roles in establishing the correct epigenetic landscape of the zygote upon fertilization, in preserving genome integrity and in initiating new patterns of genome expression that drive early mouse development.