通过对循环因子的有针对性的绑定来控制在本地位点的远程基因组相互作用
Wulan Deng1, Jongjoo Lee, Hongxin Wang
1Division of Hematology, The Children's Hospital of Philadelphia, PA 19104, USA.
Cell
|June 12, 2012
概括
即使没有 GATA1 转录因子,Ldb1 蛋白质也可以通过形成染色体循环来激活基因转录. 这一发现突出了Ldb1的重要性.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 基因规则 基因规则
背景情况:
- 染色素环连接增强剂和促进剂,但它们的结构和转录中的作用尚未完全理解.
- 在红色素细胞中,位置控制区域 (LCR) 和β-环球蛋白促进体形成了一个依赖GATA1和Ldb1.1的循环.
研究的目的:
- 研究Ldb1在形成染色质环和调节β-环球蛋白基因转录中的作用.
- 确定Ldb1是否可以独立于GATA1.1激活转录.
主要方法:
- 使用人工指 (ZF) 将Ldb1与GATA1缺陷红细胞中的β-环球蛋白促进体结合起来.
- 使用ZF-Ldb1结构评估β-环球蛋白基因激活和染色质循环形成.
- 检查了ZF-Ldb1活动的LCR要求.
主要成果:
- 在没有GATA1.1的情况下,将Ldb1向β-环球蛋白促进体激活转录.
- 与促进子绑定的Ldb1与LCR形成染色质环,招募RNA聚合酶II.
- ZF-Ldb1的活性取决于LCR的存在,这证实了需要长距离相互作用.
结论:
- Ldb1是GATA1介导的染色质循环形成的关键作用因子.
- 染色体循环是基因调节的关键机制,Ldb1的作用证明了这一点.
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