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

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.

Target practice: aiming at satellite repeats with DNA minor groove binders.

Much progress has been made in recent years in developing small molecules that target the minor groove of DNA. Striking advances have led to the design of synthetic molecules that recognize specific DNA sequences with affinities comparable to those of eukaryotic transcription factors. This makes it feasible to modulate or inhibit DNA/protein interactions in vivo, a major step towards the development of general strategies of anti-gene therapy.

Modification of position-effect variegation by competition for binding to Drosophila satellites.

White-mottled (w(m4)) position-effect variegation (PEV) arises by translocation of the white gene near the pericentric AT-rich 1.688 g/cm3 satellite III (SATIII) repeats of the X chromosome of Drosophila. The natural and artificial A*T-hook proteins D1 and MATH20 modify w(m4) PEV in opposite ways.

The AT-hook protein D1 is essential for Drosophila melanogaster development and is implicated in position-effect variegation.

We have analyzed the expression pattern of the D1 gene and the localization of its product, the AT hook-bearing nonhistone chromosomal protein D1, during Drosophila melanogaster development. D1 mRNAs and protein are maternally contributed, and the protein localizes to discrete foci on the chromosomes of early embryos. These foci correspond to 1.