RNF12是X染色体无活化X染色体的X编码的剂量依赖激活剂
Iris Jonkers1, Tahsin Stefan Barakat, Eskeatnaf Mulugeta Achame
1Department of Reproduction and Development, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands.
Cell
|December 1, 2009
概括
研究人员确定了RNF12,一种E3泛素酶,作为X染色体失活 (XCI) 的关键激活剂. 它的剂量会影响胎盘哺乳动物的XCI启动,影响基因剂量补偿.
科学领域:
- 遗传学 是一个遗传学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 哺乳动物发展 哺乳动物发展
背景情况:
- 在胎盘哺乳动物中,X染色体不活化 (XCI) 均等化了两性之间的基因剂量.
- XCI启动是一个由X编码因子调节的随机过程.
研究的目的:
- 为了确定X染色体失活的新型激活剂.
- 阐明RNF12在XCI启动中的作用.
主要方法:
- 在雄性和雌性小鼠胚胎干细胞 (ESC) 中,小鼠和人类RNF12的过度表达.
- 在RNF12转基因细胞和Rnf12异体ESC中XCI启动的分析.
- 评估RNF12的开放式读取完整性和表达水平.
主要成果:
- 增加的RNF12拷贝触发了男性ESC中的XCI和女性ESC中的双 XCI.
- RNF12的XCI启动活性取决于其开放的读取框架和表达水平.
- 在区分雌性异质合体Rnf12(+/-) ESC时,XCI启动减少.
结论:
- RNF12被确定为一个关键的XCI激活剂.
- 在XCI计数和启动过程中,RNF12具有剂量依赖的作用.
- 这一发现为X染色体剂量补偿的分子机制提供了新的见解.
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