Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
Cell Rep. 2018 Jan 2;22(1):206-217. doi: 10.1016/j.celrep.2017.11.105.
Drosophila imaginal disc cells exhibit a remarkable ability to convert cell fates in response to various perturbations, a phenomenon called transdetermination (TD). We previously identified winged eye (wge) as a factor that induces eye-to-wing TD upon overexpression in eye imaginal discs, but the molecular mechanisms underlying TD have remained largely unclear. Here, we found that wge induces various histone modifications and enhances the methylation of Lys9 on histone H3 (H3K9), a feature of heterochromatin. A histone methyltransferase, Su(var)3-9, is required for wge-mediated H3K9 methylation and eye-to-wing TD. Su(var)3-9 is also required for classical wound-induced TD but not for normal development, suggesting its involvement in several types of imaginal disc TDs. Transcriptome analysis revealed that wge represses eye identity genes independently of Su(var)3-9 and activates TD-related genes by acting together with Su(var)3-9. These findings provide new insights into diverse types of chromatin regulation at progressive steps of cell-fate conversions.
果蝇的 imaginal disc 细胞表现出一种非凡的能力，可以响应各种干扰来转换细胞命运，这种现象称为转决定（TD）。我们之前发现，winged eye（wge）在眼睛 imaginal disc 中过表达时会诱导眼睛到翅膀的 TD，是一个诱导因子，但 TD 的分子机制在很大程度上仍不清楚。在这里，我们发现 wge 诱导各种组蛋白修饰，并增强组蛋白 H3 上赖氨酸 9 的甲基化（H3K9），这是异染色质的一个特征。一个组蛋白甲基转移酶 Su(var)3-9，是 wge 介导的 H3K9 甲基化和眼睛到翅膀 TD 所必需的。Su(var)3-9 也需要用于经典的伤口诱导 TD，但不是正常发育，这表明它参与了几种 imaginal disc TD。转录组分析表明，wge 独立于 Su(var)3-9 抑制眼睛身份基因，并通过与 Su(var)3-9 一起作用激活 TD 相关基因。这些发现为细胞命运转换的渐进步骤中的多种染色质调控提供了新的见解。
