Lamin B1 controls oxidative stress responses via Oct-1

Interactions 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)...

全面介绍

书目详细资料
Main Authors: Malhas, A, Lee, C, Vaux, D
格式: Journal article
语言:English
出版: Rockefeller University Press 2009
主题:
实物特征
总结:Interactions 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 Lmnb1<sup>Δ/Δ</sup> cells. We show that several Oct-1-dependent genes, including a subset involved in oxidative stress response, are dysregulated in mnb1<sup>Δ/Δ</sup> 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 <sup>-/-</sup> cells, Lmnb1<sup>Δ/Δ</sup> 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.