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 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).
Janssen
S
S
Department of Biochemistry, University of Geneva 30, Quai Ernest-Ansermet 1211 4, Geneva, Switzerland.
Cuvier
O
O
Müller
M
M
Laemmli
U K
UK
D020856:AT Rich Sequence / Q000235:genetics; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004276:DNA, Satellite / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D005123:Eye / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005799:Genes, Dominant / Q000235:genetics; D005801:Genes, Homeobox / Q000235:genetics; D017344:Genes, Insect / Q000235:genetics*; D018398:Homeodomain Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009757:Nylons / Q000378:metabolism / Q000494:pharmacology*; D010641:Phenotype; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism
D002843:Chromatin; D004276:DNA, Satellite; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009757:Nylons; D014157:Transcription Factors; C063460:Trl protein, Drosophila