Specific gain- and loss-of-function phenotypes induced by satellite-specific DNA-binding drugs fed to Drosophila melanogaster

DNA-binding pyrrole-imidazole compounds were synthesized that target different Drosophila melanogaster satellites. Compound P31 specifically binds the GAGAA satellite V, and P9 targets the AT-rich satellites I and III. Remarkably, these drugs, when fed to developing Drosophila flies, caused gain- or...

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Bibliographic Details
Published in:Molecular cell 2000-11, Vol.6 (5), p.1013-1024
Main Authors: Janssen, S, Cuvier, O, Müller, M, Laemmli, U K
Format: Article
Language:English
Subjects:
Alleles
Animals
AT Rich Sequence - genetics
Base Sequence
Cell Nucleus - drug effects
Cell Nucleus - metabolism
Chromatin - chemistry
Chromatin - drug effects
Chromatin - genetics
Chromatin - metabolism
DNA, Satellite - genetics
DNA, Satellite - metabolism
DNA-Binding Proteins - metabolism
DNA-Binding Proteins - pharmacology
Drosophila melanogaster
Drosophila melanogaster - cytology
Drosophila melanogaster - drug effects
Drosophila melanogaster - genetics
Drosophila melanogaster - growth & development
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Eye - drug effects
Eye - growth & development
Eye - metabolism
Gene Expression Regulation, Developmental - drug effects
Genes, Dominant - genetics
Genes, Homeobox - genetics
Genes, Insect - genetics
Homeodomain Proteins - metabolism
Mutation - genetics
Nylons - metabolism
Nylons - pharmacology
Phenotype
polyamides
Substrate Specificity
Transcription Factors - metabolism
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Summary:DNA-binding pyrrole-imidazole compounds were synthesized that target different Drosophila melanogaster satellites. Compound P31 specifically binds the GAGAA satellite V, and P9 targets the AT-rich satellites I and III. Remarkably, these drugs, when fed to developing Drosophila flies, caused gain- or loss-of-function phenotypes. While polyamide P9 (not P31) suppressed PEV of white-mottled flies (increased gene expression), P31 (not P9) mediated three well-defined, homeotic transformations (loss-of-function) exclusively in brown-dominant flies. Both phenomena are explained at the molecular level by chromatin opening (increased accessibility) of the targeted DNA satellites. Chromatin opening of satellite III by P9 is proposed to suppress PEV of white-mottled flies, whereas chromatin opening of satellite V by P31 is proposed to create an inopportune "sink" for the GAGA factor (GAF).
ISSN:1097-2765
DOI:10.1016/s1097-2765(00)00100-3