View the Current Issue

Article

  • The EMBO Journal (2006) 25, 2397 - 2408
  • doi:10.1038/sj.emboj.7601125

Published online: 4 May 2006

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

Roxane Blattes1,a, Caroline Monod1,a, Guillaume Susbielle1, Olivier Cuvier2, Jian-hong Wu3, Tao-shih Hsieh3, Ulrich K Laemmli4 and Emmanuel Käs1

  1. Laboratoire de Biologie Moléculaire Eucaryote, UMR 5099 CNRS-Université Paul Sabatier, Toulouse Cedex, France
  2. Institut de Génétique Humaine, CNRS UPR 1142, Montpellier Cedex, France
  3. Department of Biochemistry, Nanaline H Duke Building, Duke University Medical Center, Durham, NC, USA
  4. Département de Biologie Moléculaire, Université de Genève, Sciences II, Geneva, Switzerland

Correspondence to:

Emmanuel Käs, LBME, UMR5099, IBCG, 118 route de Narbonne, 31062 Toulouse Cedex 9, France. Tel.: +33 561 335959; Fax: +33 561 335886; E-mail: kas@ibcg.biotoul.fr

aThese authors contributed equally to this work

Received 21 October 2005; Accepted 11 April 2006

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.

  • Keywords:

    • D1,
    • heterochromatin,
    • HP1,
    • topoisomerase II,
    • 1.688 g/cm3 satellite