基因促进者的结构进化是由灵长类特定的KRAB指蛋白驱动的
Grace Farmiloe1,2, Elisabeth J van Bree1,2, Stijn F Robben1
1Swammerdam Institute for Life Sciences, Evolutionary Neurogenomics, University of Amsterdam, Amsterdam, The Netherlands.
Genome biology and evolution
|October 17, 2023
概括
克鲁佩尔相关盒 (KRAB) 指蛋白 (KZNFs) 调节基因,除了抑制可转移元素的作用之外. 这项研究揭示了KZNFs.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 进化生物学 进化生物学
背景情况:
- 众所周知,克鲁佩尔相关盒 (KRAB) 指蛋白 (KZNFs) 抑制可转移元素 (TE),即移动DNA序列.
- KZNFs在基因调节中发挥作用,可能通过与作为增强剂和促进剂的TEs相互作用.
- 一些KZNF也直接与基因促进体结合,这表明它在TE控制之外的基因调节中起着更广泛的作用.
研究的目的:
- 调查KZNFs在基因调节中的更广泛的作用,超出它们在抑制可转移元素中的已知的功能.
- 了解KZNFs用于TE识别的结构演变如何影响它们与基因促进体的结合.
- 为基因中介KZNF基因调控功能的全基因组共选提供证据.
主要方法:
- 对特定的KZNF (ZNF519,ZNF441,ZNF468) 的结合点分析,以确定它们的目标.
- 对基因促进体内KZNF结合位点的序列转换率的分析.
- 在CRISPR/Cas9中介的基因中删除KZNF基因,以评估它们对基因表达的影响.
- 通过KZNF过度表达实验,证实它们作为基因调节者的作用.
主要成果:
- 对KZNF结合部位的分析表明,TE识别的结构进化可以导致TE序列独立于基因促进体的结合.
- 由KZNFs结合的基因促进区表现出更高的序列周转率,表明选择性压力.
- 特定的KZNFs的CRISPR/Cas9中介淘汰导致绑定基因的表达变化,特别是在神经元系.
- 过度表达KZNF证实了它们作为基因调节者的功能.
结论:
- KZNFs是真正的基因调节器,在全基因组基因调节中发挥着重要作用,超出了可移植元素控制范围.
- 这项研究提供了证据,证明KZNFs在基因调节网络中的合作,可能是由古代逆转录病毒入侵形成的.
- 基因促进体的KZNF结合位处于选择性压力之下,突出显示了它们在基因调节中的功能重要性.
- 这项研究提供了对进化过程的见解,这些进化过程将宿主防御机制整合到复杂的基因调节网络中.
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