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...

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Bibliographic Details
Published in:Molecular cell 2000-11, Vol.6 (5), p.999-1011
Main Authors: Janssen, S, Durussel, T, Laemmli, U K
Format: Article
Language:English
Subjects:
Animals
AT Rich Sequence - genetics
Base Sequence
Binding Sites
Cell Nucleus - drug effects
Cell Nucleus - metabolism
Chromatin - chemistry
Chromatin - drug effects
Chromatin - genetics
Chromatin - metabolism
Deoxyribonuclease I - metabolism
Dimerization
DNA Footprinting
DNA Topoisomerases, Type II - metabolism
DNA, Satellite - chemistry
DNA, Satellite - drug effects
DNA, Satellite - genetics
DNA, Satellite - metabolism
DNA-Binding Proteins - chemical synthesis
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - metabolism
DNA-Binding Proteins - pharmacology
Drosophila melanogaster
Drosophila melanogaster - cytology
Drosophila melanogaster - drug effects
Drosophila melanogaster - genetics
Fluorescence
Molecular Conformation
Molecular Sequence Data
Nylons - chemical synthesis
Nylons - chemistry
Nylons - metabolism
Nylons - pharmacology
Oligopeptides - chemical synthesis
Oligopeptides - chemistry
Oligopeptides - metabolism
Oligopeptides - pharmacology
Phenotype
polyamides
pyrroles
Substrate Specificity
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Summary: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.
ISSN:1097-2765
DOI:10.1016/s1097-2765(00)00099-x