在受精卵细胞中启动父基因组重编程
Lan-Tao Gou1, Do-Hwan Lim1, Wubin Ma2
1Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Cell
|March 15, 2020
概括
在受精后通过化蛋白质激酶SRPK1启动蛋白质胺与基因组的交换. 这种酸化对父母基因组重编程和早期发育中的染色质重组至关重要.
科学领域:
- 生殖生物学
- 分子生物学
- 表观遗传学
背景情况:
- 精子紧缩涉及蛋白质蛋白替代组织蛋白,这必须在受精时逆转以进行基因组重编程.
- 正确的分子机制启动和调节这种必不可少的原氨酸-氨酸交换仍然在很大程度上是未知的.
研究的目的:
- 确定在受精卵细胞中启动原氨酸与氨酸交换的关键分子参与者和机制.
- 阐明接激酶SRPK1在生命早期这一基本事件中的作用.
主要方法:
- 特定地点的化试验.
- 质氨酸凝聚和DNA依赖相变的分析.
- 核胺 (NPM2) 和HIRA招募研究.
- 在精子,卵细胞和早期前核中进行全基因组ATAC-seq分析.
主要成果:
- 拼接激酶SRPK1催化了特定位点的原氨酸酸化,从而启动了原氨酸与海斯的交换.
- 通过SRPK1介导的化促进了由NPM2和HIRA招募H3.3沉积的质氨酸排放.
- 在前核形成过程中,SRPK1的原氨酸酸化导致双亲基因组的选择性染色质可访问性被删除.
结论:
- SRPK1是原氨酸与基因组交换的关键启动者,对于精子脱凝和基因组重编程至关重要.
- 通过SRPK1进行的原胺酸化在受精后的父性和母性基因组中协调了染色质重组程序.
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