Die physiologische Funktion der Fe(II) und 2-Oxoglutarat abhängigen Dioxygenase Jmjd6 in C.elegans
Zusammenfassung der Projektergebnisse
With this proposal we have shown that the Jmjd6-homolog psr-1 is predominatly expressed in specific neurons in C.elegans, especially the PVQL and the PVQM-neurons. It is localised in the nucleus. Upon hypoxia it is up-regulated and also expressed in muscle cells. This is consistent with the presence of a conserved HIF-response element in its 5’promoter region. In early embryos we also detected expression in muscle cells. It can be speculated that this is due to the differences in oxygen availability in embryos in comparison with later larval stages and adults. In accordance with recently published data by Neumann et al indicating a function for Jmjd6 in worms for axon fusion after transection in the PLM and PLN neurons we found that the psr-1 gene is mainly expressed in neurons (the ones we could identify were the PVQL and PVQM-neurons). Our GFP-pulldown experiments were carried out with worms expressing the PSR-GFP fusion protein from a fosmid providing the endogenous regulatory elements. Expression was found in nuclei of only a few cells. Therefore the yield of PSR-GFP and possible interacting proteins after GFP-pulldown of PSR was low and we can at this point not speculate about the molecular function of C-elegans PSR in comparison with mammalian PSR. We did however detect one SR-like protein that is the best investigated mammalian Jmjd6 interacting protein so far, namely U2AF65 and a number of non-SR related proteins that we had also sometimes found in Jmjd6-pulldown experiments in mammalian cells. It could thus be worth persuing this line of investigation in invertebrate model organisms. Psr-1 did not appear consistently to be required for embryonic development, also not under hypoxic conditions. However, it is possible that an environmental condition providing oxygen, temperature or mineral deficiency stress could be identified which would increase embryonic lethality considerably. For the future, we suggest not to continue this work with C.elegans. To look at the Jmjd6 function in invertebrates we will now turn back to Hydra, which is the model organism where our group is usually working with. We will suggest in a new proposal to make an antibody against Hydra-Jmjd6 and a transgenic hydra-line overexpressing Jmjd6-GFP. We will then try to find the Jmjd6-interacting proteins in hydra and also study the localisation of the endogenous protein as well as answer the question whether it is induced under hypoxic conditions.
Projektbezogene Publikationen (Auswahl)
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The oxygenase Jmjd6-a case study in conflicting assignments, Biochem. J. 468 (2), p 191-202, 2015
Böttger, A., Islam, M.S., Chowdhury, R., Schofield, C.J., Wolf, A.
