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

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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.