Functional analysis of Jumonji/Jarid2 in Drosophila melanogaster

キイロショウジョウバエJumonji/Jarid2の機能解析

2018-03-26

2018-03-26

Jumonji (Jmj)/Jarid2 is a nuclear protein that has multiple functions in controlling cell proliferation and regulating chromatin structure. Recent finding in mammalian cells identified Jmj as a component of Polycomb repressive complex 2 (PRC2), which functions in repressing gene expression via histone modification. However, many questions on function of Jmj not related to PRC2 still remains. In this thesis, to further clarify the unknown function of Jmj, I used Drosophila melanogaster model to analyze the function of Drosophila Jmj (dJmj). dJmj has been suggested to have both PRC-dependent and -independent roles. In the late growth stage of Drosophila spermatogenesis, I found dJmj exclusively localizes at nucleolus and testis-specific TAF homolog is responsible for recruitments of dJmj to nucleolus that appears to be mediated by some of Polycomb group (PcG) genes. Duolink In situ Proximity ligation assay clarified that Polycomb interacts with dJmj at nucleolus in the late growth stage. Furthermore, the level of tri-methylation of histone H3 lysine 27 (H3K27me3), likely representing PRC2 activity, decreased in nuclei at this stage. Compartmentalization of dJmj in nucleolus together with some of PcG may be necessary to derepress the expression of genes required to cellular growth and proliferation in the following meiotic divisions. In contrast, study in Drosophila adult intestinal stem cell system suggested PRC2-independent roles of dJmj. Overexpression of dJmj in intestinal stem cells induced their proliferation. Conversely, overexpression of dJmj in differentiated cells promoted their apoptosis and then activated the proliferation of stem cells via some feedback signaling pathways. Surprisingly, these effects did not relate to H3K27me3 status in dJmj-overexpressing cells. Instead of this, the disappearance of H3K27me3 in differentiated cells after stem cell-specific overexpression of dJmj suggested a possible role of dJmj in regulating chromatin structure. Taken together, these findings indicated different functions of dJmj in different tissues, which dependent or independent with PcG proteins, and demonstrated the context- and demand-specific functions of Jmj.

博士（学術）

京都工芸繊維大学

14303甲第867号

http://hdl.handle.net/10212/2462

eng

ETD

Thesis or Dissertation

Thesis