Inheritance of Stress-Induced, ATF-2-dependent Epigenetic Change

Cell. 2011 Jun 24;145(7):1049-61. doi: 10.1016/j.cell.2011.05.029.

Abstract

Atf1, the fission yeast homolog of activation transcription factor-2 (ATF-2), contributes to heterochromatin formation. However, the role of ATF-2 in chromatin assembly in higher organisms remains unknown. This study reveals that Drosophila ATF-2 (dATF-2) is required for heterochromatin assembly, whereas the stress-induced phosphorylation of dATF-2, via Mekk1-p38, disrupts heterochromatin. The dATF-2 protein colocalized with HP1, not only on heterochromatin but also at specific loci in euchromatin. Heat shock or osmotic stress induced phosphorylation of dATF-2 and resulted in its release from heterochromatin. This heterochromatic disruption was an epigenetic event that was transmitted to the next generation in a non-Mendelian fashion. When embryos were exposed to heat stress over multiple generations, the defective chromatin state was maintained over multiple successive generations, though it gradually returned to the normal state. The results suggest a mechanism by which the effects of stress are inherited epigenetically via the regulation of a tight chromatin structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 2 / analysis
  • Activating Transcription Factor 2 / genetics
  • Activating Transcription Factor 2 / metabolism*
  • Animals
  • Drosophila Proteins / analysis
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / metabolism
  • Epigenomics
  • Euchromatin / metabolism
  • Female
  • Heterochromatin / chemistry
  • Heterochromatin / metabolism*
  • MAP Kinase Kinase Kinase 1 / metabolism
  • Male
  • Mutagenesis
  • Phosphorylation
  • Signal Transduction
  • Stress, Physiological
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • ATF-2 protein, Drosophila
  • Activating Transcription Factor 2
  • Drosophila Proteins
  • Euchromatin
  • Heterochromatin
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1