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在SCNT介导的ZGA过程中,Setd2过度表达拯救了双价基因表达

Xiaolei Zhang^1,2, Ruimin Xu^1,2, Yuyan Zhao^1,2

¹Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Med-icine and Gynecologic Oncology, Clinical and Translation Research Center, Shanghai First Ma-ternity and Infant Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China.

|February 13, 2025

概括

克服克隆中的表观遗传障碍是关键. 在克隆胚胎中提高H3K36me3水平可以消除异常的表观遗传标记,显著提高克隆效率.

科学领域:

表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
发展生物学发展生物学
生殖科学生殖科学

背景情况:

体细胞核转移 (SCNT) 克隆受到表观遗传重编程障碍的阻碍.
基质子修饰,特别是H3K4me3和H3K27me3,与这些SCNT挑战有关.
这些表观遗传标记阻碍克隆的确切机制在很大程度上仍未确定.

研究的目的:

为了研究H3K4me3和H3K27me3在小鼠植入前克隆胚胎中的全基因组分布.
阐明异常表观遗传标记在SCNT介导的发育错误中的作用.
通过操纵表观遗传景观来确定提高克隆效率的策略.

主要方法:

在小鼠克隆 (NT) 和自然受精 (NF) 胚胎中生成全基因组H3K4me3和H3K27me3图.
基斯顿标记分布和双价促销物状态的定量分析.
在克隆胚胎中,H3K36me3甲基转移酶Setd2的过度表达.

主要成果:

与NF胚胎相比,克隆胚胎在基因促进者中表现出增加的双价标记 (H3K4me3/H3K27me3),与减少的H3K36me3.3相关.
Setd2的过度表达使H3K36me3水平正常化,纠正了异常的H3K4me3和H3K27me3模式,并恢复了ZGA基因表达.
在基因体中恢复H3K36me3减少了双价促销器标记,从而改善了克隆结果.

结论:

过度的双价促体状态是SCNT克隆成功的重要障碍.
通过针对性地操纵H3K36me3,例如通过Setd2,可以解决这些表观遗传障碍.
增强H3K36me3是一种有前途的策略,可以提高体细胞核转移克隆的效率.

关键词:

这是SCNT.胚胎发育过程中的胚胎发育.基质子的修改基质子的修改

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