Department of Applied Biology, The Center for Advanced Insect Research, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Department of Molecular Biology, College of Pharmacy, Longevity Life Science and Technology Institutes, Pusan National University, Busan 609-735, Republic of Korea.
Cell Signal. 2018 Jan;42:194-210. doi: 10.1016/j.cellsig.2017.10.017. Epub 2017 Nov 2.
Jumonji (Jmj)/Jarid2 is a DNA-binding transcriptional repressor mediated via histone methylation. Nevertheless, the well-known function of Jmj is as a scaffold for the recruitment of various complexes including Polycomb repressive complex 2 (PRC2), and required for mouse embryonic stem cell development. However, PRC2 independent function is suggested for Drosophila Jumonji (dJmj). To clarify the function of dJmj during cell differentiation, we used Drosophila adult intestinal stem cell system that allows to follow stem cell behaviors in vivo. Overexpression of dJmj in intestinal stem cells/enteroblasts (ISCs/EBs) induces cell-autonomous ISC proliferation followed by differentiation, that is controlled by the Notch and EGFR pathway. In contrast, overexpression of dJmj in enterocytes (ECs) resulted in activation of the JNK pathway in ECs followed by the induction of apoptosis. Activated JNK increased the level of Yorkie in ECs and induced the reduction of Upd proteins and EGFR ligands, which activated the JAK/STAT and EGFR pathway in both ISCs and EBs to promote ISC proliferation. The Notch signaling pathway appears to be highly activated to support the differentiation of EBs to ECs. Thus, the combination of these signaling pathways caused by ECs-specific dJmj-overexpression induced non-cell-autonomous ISC proliferation and differentiation. Surprisingly, these effects did not relate to H3K27me3 status, likely represented PRC2 activity, in cells that overexpressed dJmj. Instead of this, the disappearance of H3K27me3 in ISC/EB-specific overexpressed dJmj suggested a possible PRC2-independent role of dJmj in regulating chromatin structure.
Jumonji (Jmj)/Jarid2 是一种通过组蛋白甲基化介导的 DNA 结合转录抑制因子。然而，Jmj 的已知功能是作为各种复合物（包括 Polycomb 抑制复合物 2 (PRC2)）招募的支架，对于小鼠胚胎干细胞的发育是必需的。然而，果蝇 Jumonji (dJmj) 表现出 PRC2 非依赖性功能。为了阐明 dJmj 在细胞分化过程中的功能，我们利用了果蝇成年肠道干细胞系统，该系统允许在体内跟踪干细胞行为。在肠道干细胞/肠母细胞 (ISCs/EBs) 中过度表达 dJmj 会诱导细胞自主的 ISC 增殖，随后是由 Notch 和 EGFR 途径控制的分化。相比之下，在肠细胞 (ECs) 中过度表达 dJmj 会导致 EGFR 途径的 JNK 通路激活，随后诱导凋亡。激活的 JNK 增加了 ECs 中 Yorkie 的水平，并诱导 Upd 蛋白和 EGFR 配体的减少，这激活了 ISCs 和 EBs 中的 JAK/STAT 和 EGFR 途径，促进 ISC 增殖。Notch 信号通路似乎高度激活以支持 EBs 分化为 ECs。因此，由 ECs 特异性 dJmj 过表达引起的这些信号通路的组合导致了非细胞自主的 ISC 增殖和分化。令人惊讶的是，这些效应与细胞中过表达 dJmj 的 H3K27me3 状态无关，可能代表 PRC2 活性。相反，在 ISC/EB 特异性过表达 dJmj 中 H3K27me3 的消失表明 dJmj 在调节染色质结构中可能具有 PRC2 非依赖性作用。
