Lamin B1 controls oxidative stress responses via Oct-1.
Lamin B1 controls oxidative stress responses via Oct-1.
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DOI：
10.1083/jcb.200804155
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发表时间：
2009-01-12
期刊：
影响因子：
--
通讯作者：
Vaux DJ
中科院分区：
文献类型：
--
作者：
Malhas AN;Lee CF;Vaux DJ
核纤层蛋白与染色质和转录因子的相互作用调节转录。Oct-1先前已被证明与B型核纤层蛋白部分共定位，并且对于氧化应激反应基因的转录调节是必需的。使用顺序提取，免疫共沉淀（IP），光漂白中的荧光损失和荧光共振能量转移，我们证实了Oct-1-核纤层蛋白B1在核周围的关联，并表明这种关联在Lmnb 1 Δ/Δ细胞中丢失。我们发现，几个Oct-1依赖性基因，包括参与氧化应激反应的一个子集，在Lmnb 1 Δ/Δ细胞中失调。电泳迁移率变动分析和染色质IP显示，Oct-1结合到假定的八聚体结合序列的失调基因，这种活性增加细胞缺乏功能核纤层蛋白B1。与Oct 1 −/−细胞一样，Lmnb 1 Δ/Δ细胞的活性氧水平升高，更容易受到氧化应激的影响。核纤层蛋白B1在核周围隔离Oct-1可能是核被膜调节基因表达并促进细胞对应激、发育和衰老的反应的一种机制。
Interaction of lamins with chromatin and transcription factors regulate transcription. Oct-1 has previously been shown to colocalize partly with B-type lamins and is essential for transcriptional regulation of oxidative stress response genes. Using sequential extraction, co-immunoprecipitation (IP), fluorescence loss in photobleaching, and fluorescence resonance energy transfer, we confirm Oct-1–lamin B1 association at the nuclear periphery and show that this association is lost in Lmnb1Δ/Δ cells. We show that several Oct-1–dependent genes, including a subset involved in oxidative stress response, are dysregulated in Lmnb1Δ/Δ cells. Electrophoretic mobility shift assay and chromatin IP reveal that Oct-1 binds to the putative octamer-binding sequences of the dysregulated genes and that this activity is increased in cells lacking functional lamin B1. Like Oct1−/− cells, Lmnb1Δ/Δ cells have elevated levels of reactive oxygen species and are more susceptible to oxidative stress. Sequestration of Oct-1 at the nuclear periphery by lamin B1 may be a mechanism by which the nuclear envelope can regulate gene expression and contribute to the cellular response to stress, development, and aging.
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