Chromatin opening of DNA satellites by targeted sequence-specific drugs.
There are few tools available for dissecting and elucidating the functions of DNA satellites and other nongenic DNA. To address this, we have explored the experimental potential of DNA sequence-specific drugs containing pyrrole and imidazole amino acids (polyamides). Compounds were synthesized that target different Drosophila melanogaster satellites. Dimeric oligopyrroles were shown to target the AT-rich satellites I, III, and SARs (scaffold associated regions). One polyamide (P31) specifically binds the GAGAA satellite V. Specificity of targeting was established by footprinting, epifluorescence of nuclei, and polytene chromosomes stained with fluorescent derivatives. These polyamides were shown to mediate satellite-specific chromatin opening of the chromatin fiber. Remarkably, certain polyamides induced defined gain or loss-of-function phenotypes when fed to Drosophila melanogaster.
Janssen
S
S
Departments of Biochemistry and Molecular Biology University of Geneva 30, Quai Ernest-Ansermet 1211 4, Geneva, Switzerland.
Durussel
T
T
Laemmli
U K
UK
D020856:AT Rich Sequence / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry* / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018983:DNA Footprinting; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004276:DNA, Satellite / Q000737:chemistry* / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003850:Deoxyribonuclease I / Q000378:metabolism; D019281:Dimerization; D004331:Drosophila melanogaster / Q000166:cytology / Q000187:drug effects / Q000235:genetics; D005453:Fluorescence; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010641:Phenotype; D013379:Substrate Specificity
D002843:Chromatin; D004276:DNA, Satellite; D004268:DNA-Binding Proteins; D009757:Nylons; D009842:Oligopeptides; D003850:Deoxyribonuclease I; D004250:DNA Topoisomerases, Type II