Displacement of D1, HP1 and topoisomerase II from satellite heterochromatin by a specific polyamide

EMBO J. 2006 Jun 7;25(11):2397-408. doi: 10.1038/sj.emboj.7601125. Epub 2006 May 4.


The functions of DNA satellites of centric heterochromatin are difficult to assess with classical molecular biology tools. Using a chemical approach, we demonstrate that synthetic polyamides that specifically target AT-rich satellite repeats of Drosophila melanogaster can be used to study the function of these sequences. The P9 polyamide, which binds the X-chromosome 1.688 g/cm3 satellite III (SAT III), displaces the D1 protein. This displacement in turn results in a selective loss of HP1 and topoisomerase II from SAT III, while these proteins remain bound to the adjacent rDNA repeats and to other regions not targeted by P9. Conversely, targeting of (AAGAG)n satellite V repeats by the P31 polyamide results in the displacement of HP1 from these sequences, indicating that HP1 interactions with chromatin are sensitive to DNA-binding ligands. P9 fed to larvae suppresses the position-effect variegation phenotype of white-mottled adult flies. We propose that this effect is due to displacement of the heterochromatin proteins D1, HP1 and topoisomerase II from SAT III, hence resulting in stochastic chromatin opening and desilencing of the nearby white gene.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AT Rich Sequence
  • Animals
  • Base Sequence
  • Brain / physiology
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Topoisomerases, Type II / genetics
  • DNA Topoisomerases, Type II / metabolism*
  • DNA, Satellite / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian / anatomy & histology
  • Embryo, Nonmammalian / physiology
  • Embryonic Structures / physiology
  • Female
  • Heterochromatin / genetics*
  • Heterochromatin / metabolism
  • Molecular Sequence Data
  • Nylons / chemistry
  • Nylons / metabolism*
  • Photoreceptor Cells, Invertebrate / anatomy & histology
  • Photoreceptor Cells, Invertebrate / physiology


  • Chromosomal Proteins, Non-Histone
  • D1 protein, Drosophila
  • DNA, Satellite
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Heterochromatin
  • Nylons
  • heterochromatin protein 1, Drosophila
  • DNA Topoisomerases, Type II