在印记控制区域H19/Igf2建立父亲甲基化印记
Ji Liao1, Sangmin Song2, Samuel Gusscott3
1Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.
Science advances
|September 6, 2023
概括
通过H19/Igf2印记控制区域 (ICR) 的低水平转录对于在男性生殖细胞中建立父性甲基化印记至关重要. 干扰导致异常印记,影响胎儿生长,并可能导致银-拉塞尔综合征.
科学领域:
- 遗传学和表观遗传学
- 发展生物学 发展生物学
背景情况:
- H19/Igf2印记域使用了涉及CTCF的绝缘体模型,用于体细胞中母系和父系等位基因之间的差异基因表达.
- 在男性生殖系的印记控制区域 (ICR) 建立父亲甲基化印记的精确分子机制尚不清楚.
研究的目的:
- 为了研究繁荣的特异性转录在建立在H19/Igf2 ICR的父性甲基化印记中的作用.
- 确定通过ICR中断转录对印记,基因表达和胎儿发育的影响.
主要方法:
- 利用小鼠基因来操纵和研究H19/Igf2 ICR入口点中的转录水平.
- 分析了在生殖细胞和体细胞中建立和持久的父亲甲基化印记.
- 评估胎儿器官中的Igf2表达水平和评估胎儿生长参数.
主要成果:
- 当通过ICR抑制转录时,观察到异常的父亲印记建立.
- 由此产生的生殖系表延续在体细胞的父方等位基因中.
- 胎儿器官中的Igf2表达减少和胎儿生长减少与绝缘体模型和IGF2在胎儿发育中的作用一致.
结论:
- 通过H19/Igf2 ICR进行广泛的低水平转录对于在男性生殖系中建立父性甲基化印记至关重要.
- 这种转录的破坏会导致遗传性表,对胎儿生长产生表型后果.
- 这些发现有助于理解印记障碍,如银-拉塞尔综合征.
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