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是通过组蛋白甲基化介导的DNA结合转录阻遏物。尽管如此，Jmj的众所周知的功能是作为募集各种复合物（包括Polycomb抑制复合物2（PRC2））的支架，并且是小鼠胚胎干细胞发育所必需的。但是，建议果蝇Jumonji（dJmj）的PRC2独立功能。为了阐明dJmj在细胞分化过程中的功能，我们使用了果蝇成人肠道干细胞系统，可以追踪体内干细胞的行为。dJmj在肠干细胞/成胚细胞（ISC / EBs）中的过表达诱导细胞自主ISC增殖，然后分化，这受Notch和EGFR途径控制。相反，dJmj在肠上皮细胞（ECs）中的过表达导致ECs中JNK途径的激活，然后诱导凋亡。活化的JNK增加EC中约克的水平并诱导Upd蛋白和EGFR配体的减少，从而激活ISC和EB中的JAK / STAT和EGFR途径，从而促进ISC增殖。Notch信号通路似乎被高度激活以支持EB向EC的分化。因此，ECs特异性dJmj过表达引起的这些信号通路的组合诱导了非细胞自主ISC增殖和分化。出乎意料的是，在过度表达dJmj的细胞中，这些作用与H3K27me3状态无关，可能代表PRC2活性。取而代之的是，ISC / EB特异表达的dJmj中H3K27me3的消失提示dJmj在调节染色质结构中可能具有不依赖PRC2的作用。