Abstract：
BACKGROUND: The Keap1-Nrf2 pathway serves as a central regulator that mediates transcriptional responses to xenobiotic and oxidative stimuli. Recent studies have shown that Keap1 and Nrf2 can regulate transcripts beyond antioxidant and detoxifying genes, yet the underlying mechanisms remain unclear. Our research has uncovered that Drosophila Keap1 (dKeap1) and Nrf2 (CncC) proteins can control high-order chromatin structure, including heterochromatin.
RESULTS: In this study, we identified the molecular interaction between dKeap1 and lamin Dm0, the Drosophila B-type lamin responsible for the architecture of nuclear lamina and chromatin. Ectopic expression of dKeap1 led to an ectopic localization of lamin to the intra-nuclear area, corelated with the spreading of the heterochromatin marker H3K9me2 into euchromatin regions. Additionally, mis-regulated dKeap1 disrupted the morphology of the nuclear lamina. Knocking down of dKeap1 partially rescued the lethality induced by lamin overexpression, suggesting their genetic interaction during development.
CONCLUSIONS: The discovered dKeap1-lamin interaction suggests a novel role for the Keap1 oxidative/xenobiotic response factor in regulating chromatin architecture.
RESULTS: In this study, we identified the molecular interaction between dKeap1 and lamin Dm0, the Drosophila B-type lamin responsible for the architecture of nuclear lamina and chromatin. Ectopic expression of dKeap1 led to an ectopic localization of lamin to the intra-nuclear area, corelated with the spreading of the heterochromatin marker H3K9me2 into euchromatin regions. Additionally, mis-regulated dKeap1 disrupted the morphology of the nuclear lamina. Knocking down of dKeap1 partially rescued the lethality induced by lamin overexpression, suggesting their genetic interaction during development.
CONCLUSIONS: The discovered dKeap1-lamin interaction suggests a novel role for the Keap1 oxidative/xenobiotic response factor in regulating chromatin architecture.
摘要：
背景：Keap1-Nrf2途径充当介导对异种生物和氧化刺激的转录反应的中央调节因子。最近的研究表明，Keap1和Nrf2可以调节抗氧化和解毒基因之外的转录本，然而，潜在的机制仍不清楚。我们的研究发现果蝇Keap1（dKeap1）和Nrf2（CncC）蛋白可以控制高级染色质结构，包括异染色质。
结果：在这项研究中，我们确定了dKeap1和LaminDm0之间的分子相互作用，Dm0是负责核层和染色质结构的果蝇B型层蛋白。dKeap1的异位表达导致层粘连蛋白异位定位到核内区域，与异染色质标记H3K9me2扩散到常染色质区域相关。此外,错误调节的dKeap1破坏了核层的形态。dKeap1的敲除部分挽救了由lamin过度表达引起的致死率，表明它们在发育过程中的遗传相互作用。
结论：发现的dKeap1-lamin相互作用提示了Keap1氧化/异种生物反应因子在调节染色质结构方面的新作用。
结果：在这项研究中，我们确定了dKeap1和LaminDm0之间的分子相互作用，Dm0是负责核层和染色质结构的果蝇B型层蛋白。dKeap1的异位表达导致层粘连蛋白异位定位到核内区域，与异染色质标记H3K9me2扩散到常染色质区域相关。此外,错误调节的dKeap1破坏了核层的形态。dKeap1的敲除部分挽救了由lamin过度表达引起的致死率，表明它们在发育过程中的遗传相互作用。
结论：发现的dKeap1-lamin相互作用提示了Keap1氧化/异种生物反应因子在调节染色质结构方面的新作用。
