The association of genomic loci to the nuclear periphery is proposed to facilitate cell type-specific gene repression and influence cell fate decisions. However, the interplay between gene position and expression remains incompletely understood, in part because the proteins that position genomic loci at the nuclear periphery remain unidentified. Here, we used an Oligopaint-based HiDRO screen targeting ∼1000 genes to discover novel regulators of nuclear architecture in Drosophila cells. We identified the heterochromatin-associated protein Stonewall (Stwl) as a factor promoting perinuclear chromatin positioning. In female germline stem cells (GSCs), Stwl binds and positions chromatin loci, including GSC differentiation genes, at the nuclear periphery. Strikingly, Stwl-dependent perinuclear positioning is associated with transcriptional repression, highlighting a likely mechanism for Stwl's known role in GSC maintenance and ovary homeostasis. Thus, our study identifies perinuclear anchors in Drosophila and demonstrates the importance of gene repression at the nuclear periphery for cell fate.

中文翻译：

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果蝇的核结构筛选将 Stonewall 确定为核外围染色质位置与生殖干细胞命运之间的联系


基因组位点与核外围的关联被提议促进细胞类型特异性基因抑制并影响细胞命运决定。然而，基因位置和表达之间的相互作用仍然不完全清楚，部分原因是将基因组位点定位在核外围的蛋白质仍未被识别。在这里，我们使用基于 Oligopaint 的 HiDRO 筛选约 1000 个基因来发现果蝇细胞核结构的新型调节因子。我们确定异染色质相关蛋白 Stonewall (Stwl) 是促进核周染色质定位的因素。在雌性生殖干细胞 (GSC) 中，Stwl 在核周边结合并定位染色质位点，包括 GSC 分化基因。引人注目的是，Stwl 依赖性核周定位与转录抑制相关，这突显了 Stwl 在 GSC 维持和卵巢稳态中已知作用的可能机制。因此，我们的研究鉴定了果蝇的核周锚点，并证明了核外围基因抑制对细胞命运的重要性。