Masuko Keita, Furuhashi Hirofumi, Komaba Kanae, Numao Eriko, Nakajima Rumi, Fuse Naoyuki, Kurata Shoichiro
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Genes Cells. 2018 Jul 2. doi: 10.1111/gtc.12608.
Drosophila imaginal discs often change their cell fate under stress conditions, and this phenomenon, called transdetermination (TD), has long been a useful model for studying cell fate plasticity during regeneration. We previously identified a chromatin-associated protein, Winged Eye (Wge), which induces eye-to-wing TD upon its over-expression in eye imaginal discs. However, the molecular mechanism of Wge-mediated TD remains obscure. Here, we analyzed Wge-interacting proteins and found that several heterochromatin-related proteins, including a nuclear lamina protein, Lamin (Lam), were associated with Wge protein in cultured cells. Knockdown experiments revealed that Lam is indeed required for Wge-mediated eye-to-wing TD. Moreover, Wge over-expression altered the spatial organization of genomic DNA inside the cell nuclei. Accordingly, we suggest that Wge interacts with Lam to link some genomic regions with the nuclear periphery and regulates chromatin dynamics in imaginal disc TD.
果蝇成虫盘在应激条件下常常会改变其细胞命运，这种现象被称为转决定（TD），长期以来一直是研究再生过程中细胞命运可塑性的有用模型。我们之前鉴定出一种与染色质相关的蛋白，有翼眼（Wge），当其在眼成虫盘中过表达时会诱导眼到翅的转决定。然而，Wge介导的转决定的分子机制仍不清楚。在这里，我们分析了与Wge相互作用的蛋白，发现几种与异染色质相关的蛋白，包括一种核纤层蛋白，核纤层蛋白（Lam），在培养细胞中与Wge蛋白相关联。敲低实验表明，Lam确实是Wge介导的眼到翅转决定所必需的。此外，Wge的过表达改变了细胞核内基因组DNA的空间组织。因此，我们认为Wge与Lam相互作用，将一些基因组区域与核周边连接起来，并调节成虫盘转决定中的染色质动力学。
