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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 Lmnb1(Delta/Delta) cells. We show that several Oct-1-dependent genes, including a subset involved in oxidative stress response, are dysregulated in Lmnb1(Delta/Delta) 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, Lmnb1(Delta/Delta) 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.

Original publication

DOI

10.1083/jcb.200804155

Type

Journal article

Journal

J Cell Biol

Publication Date

12/01/2009

Volume

184

Pages

45 - 55

Keywords

Animals, Cells, Cultured, Cellular Senescence, Chromatin Immunoprecipitation, Electrophoretic Mobility Shift Assay, Gene Expression Regulation, Lamin Type B, Mice, Nuclear Lamina, Octamer Transcription Factor-1, Oxidative Stress, Reactive Oxygen Species