The physiological function of the Fe(II) and 2-oxo-glutarate dependent dioxygenase Jmjd6 in C. elegans

线虫中 Fe(II) 和 2-氧代戊二酸依赖性双加氧酶 Jmjd6 的生理功能

• 批准号: 253119847
• 负责人: Professorin Dr. Angelika Böttger
• 金额: --
• 依托单位: Abteilung für Zell- und Entwicklungsbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/253119847?language=en
• 关键词: physiological; function; Fe; II; oxo

Jmjd6 belongs to the Fe(II) and 2-oxoglutarate dependent dioxygenase family. These enzymes use atmospheric oxygen to hydroxylate their substrates and are thus capable of sensing oxygen tension. Jmjd6 is a lysine hydroxylase. Its specific substrates comprise ribosomal proteins and splice factors. Jmjd6 knockout or knockdown in vertebrates leads to severe developmental defects and perinatal embryonic cell death. The Jmjd6 sequence is very well conserved throughout the whole animal kingdom, however, in contrast to vertebrates, Jmjd6 knockdown in invertebrate model organisms does not have any obvious developmental phenotypes. The aim of this study is to study the function of Jmjd6 in invertebrates. Moreover, we want to find out, whether Jmjd6 is involved in the hypoxic response pathway in C. elegans. We want to analyse the phenotype of a Jmjd6 loss of function mutant and the expression pattern of Jmjd6 in C. elegans under hypoxic and normoxic conditions. Finally, we aim to conduct a GFP-pulldown experiment with Jmjd6 in C. elegans in order to find out whether in invertebrates Jmjd6 also interacts with RS-domains of splice modulators. As a result of this project we would like to develop C. elegans with its unique properties as a genetically approachable model organisms to obtain insight into the physiological function of Jmjd6 and at a larger perspective the contribution of enzymatic JmjC-domains to regulating adaptation of cellular responses to oxygen.

Jmjd 6属于Fe（II）和2-酮戊二酸依赖性双加氧酶家族。这些酶利用大气中的氧来羟基化它们的底物，因此能够感测氧张力。jmjd 6是赖氨酸羟化酶。其特异性底物包括核糖体蛋白和剪接因子。脊椎动物中jmjd 6基因敲除或敲低导致严重的发育缺陷和围产期胚胎细胞死亡。Jmjd 6序列在整个动物界中非常保守，然而，与脊椎动物相反，无脊椎动物模式生物中的Jmjd 6敲除没有任何明显的发育表型。本研究的目的是研究Jmjd 6在无脊椎动物中的功能。此外，我们还想了解Jmjd 6是否参与了C.优雅的我们希望分析Jmjd 6功能缺失突变体的表型和Jmjd 6在C.在低氧和常氧条件下的线虫。最后，我们的目标是在C中用Jmjd 6进行GFP下拉实验。elegans中，以找出是否在无脊椎动物中Jmjd 6也与剪接调节剂的RS结构域相互作用。作为这个项目的结果，我们想开发C。elegans作为遗传上可接近的模式生物的独特性质，以获得对Jmjd 6的生理功能的洞察，并从更大的角度了解酶促JmjC结构域对调节细胞对氧的反应的适应的贡献。