保存的Cis作用范围扩展元件调解了哺乳动物极端远程增强器活动
Grace Bower1, Ethan W Hollingsworth1,2, Sandra Jacinto1
1Department of Developmental and Cell Biology, University of California, Irvine, CA 92967, USA.
bioRxiv : the preprint server for biology
|June 3, 2024
概括
科学家们发现了一种新型的DNA元素 - - 范围扩展器 (REX),它使增强剂能够在超大基距离上调节基因. 这一发现解释了增强剂如何实现极端范围的基因调节,这对发育至关重要.
科学领域:
- 基因组学就是基因组学.
- 发展生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 哺乳动物增强剂通常会调节几十个基基的基因促进剂.
- 能够使增强器在超大基距离上起作用的序列特征在很大程度上是未知的.
研究的目的:
- 为了确定赋予极端距离增强器-促进器相互作用能力的序列特征.
- 通过增强剂研究长距离基因调节背后的机制.
主要方法:
- 在小鼠体内增强剂替代实验.
- 一种新型 cis 作用元素 (REX) 的鉴定和特征.
- 在ZRS增强器中对保存动机的突变分析.
主要成果:
- 短程和中程增强器在没有特定元素的情况下无法在极端距离上运行.
- 一种新的保守的cis-acting元素,范围扩展器 (REX),赋予极端距离的调节活动.
- 含有[C/T]AATTA家庭主体动机的REX元素显著扩大了增强剂相互作用范围,高达一个数量级.
- 在ZRS增强剂中突变这些基因消除了远程活性,但不能消除短程活性,从而导致四肢缺陷.
结论:
- 一个序列签名,REX元素与[C/T]AATTA动机,被确定为长距离增强剂-促进剂相互作用的关键.
- 雷克斯元素是必要的,并且足以通过远程增强器赋予极远距离的基因激活.
- 这一发现提供了对发育过程中长距离基因调节的机制的见解.
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