Analysis of histone posttranslational modifications in the control of chromatin plasticity observed at estrogen-responsive sites in human breast cancer cells

Methods Mol Biol. 2014:1204:59-69. doi: 10.1007/978-1-4939-1346-6_6.

Abstract

It is well established that histone posttranslational modifications mediate the control of gene expression played by chromatin. Such modifications are commonly reversible and many alternatives are open to drive transcription of inducible genes. Estrogens govern growth and survival of hormone-sensitive cells by inducing expression of genes important for cell cycle progression and apoptosis. Transcription of estrogen-responsive genes is triggered by the lysine-specific demethylase 1 (LSD1)-dependent demethylation of dimethylated lysine 9 in histone H3 (H3K9me2) that accompanies to local generation of oxygen reactive species (ROS). Production of ROS modifies guanines in neighbor DNA with consequent recruitment of base-excision repair (BER) enzymes and formation of breaks that support creation of bridges between sites that, although distant on linear DNA, establish strategic contacts useful for productive transcription.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation / methods
  • DNA / genetics
  • DNA / metabolism
  • Electrophoresis, Agar Gel / methods
  • Epigenesis, Genetic
  • Estrogens / metabolism*
  • Female
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • MCF-7 Cells
  • Polymerase Chain Reaction / methods
  • Protein Processing, Post-Translational

Substances

  • Chromatin
  • Estrogens
  • Histones
  • DNA