Investigating the role of evolutionary conserved KRAB-ZFPs

研究进化保守的 KRAB-ZFP 的作用

• 批准号: 2119353
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2119353
• 关键词: Investigating; role; evolutionary; conserved; KRAB

Transposable elements (TEs) of various forms and age constitute ~50% of the human genome. Given their abundance, there is less research into TE function than we would expect - this is mostly due to the widespread perception that they are mostly 'junk DNA' with no appreciable function. As such, it remains poorly understood how this half of our genome contributes to our biology.KRAB-ZFPs are the largest family of DNA binding factors in tetrapods, displaying enriched binding to TEs. They are transcriptional repressors, and many are evolutionary conserved with TE-targets that are largely degraded. However, the biological functions of many individual members of this protein family are unknown. It is thought that some of the TEs bound by KRAB-ZFPs might have been co-opted as regulatory platforms, perhaps acting as enhancers or alternative promoters.By focusing on a few KRAB-ZFPs that are conserved between humans and mouse, the aim of this PhD project is to further characterise the roles of conserved KRAB-ZFPs in the domestication of TEs for the regulation of host gene expression. In addition to better defining the biological functions of a few individual KRAB-ZFPs, we aim to reveal some general principles of how the repeat genome is functionally integrated into host genomes, and gain insight into the co-evolutionary relationship between TEs and KRAB-ZFPs.

各种形式和年龄的转座因子（TE）占人类基因组的约50%。考虑到它们的丰富性，对TE功能的研究比我们预期的要少-这主要是由于人们普遍认为它们大多是没有明显功能的“垃圾DNA”。因此，我们对这一半基因组如何对我们的生物学做出贡献仍然知之甚少。KRAB-ZFP是四足动物中最大的DNA结合因子家族，显示出与TE的富集结合。它们是转录抑制因子，并且许多是进化保守的，具有很大程度上降解的TE靶。然而，该蛋白质家族的许多个体成员的生物学功能是未知的。本博士项目的目的是通过研究人和小鼠之间保守的几种KRAB-ZFPs，进一步阐明保守的KRAB-ZFPs在驯化TE调控宿主基因表达中的作用。除了更好地定义一些单个KRAB-ZFP的生物学功能外，我们的目标是揭示重复基因组如何在功能上整合到宿主基因组中的一些一般原则，并深入了解TE和KRAB-ZFP之间的共同进化关系。