Lamin B1 controls oxidative stress responses via Oct-1

J Cell Biol. 2009 Jan 12;184(1):45-55. doi: 10.1083/jcb.200804155.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Lamin Type B
  • Octamer Transcription Factor-1
  • Reactive Oxygen Species