Specific inhibition of DNA binding to nuclear scaffolds and histone H1 by distamycin. The role of oligo(dA).oligo(dT) tracts.
Scaffold-associated regions (SARs) are A + T-rich sequences defined by their specific interaction with the nuclear scaffold. These sequences also direct highly specific binding to purified histone H1, and are characterized by the presence of oligo(dA).oligo(dT) tracts, which are a target for the drug distamyin, an antibiotic with a wide range of biological activities. The interaction of distamycin with SAR sequences results in the complete suppression of binding to either scaffolds or histone H1, suggesting that (dA.dT)n tracts play a direct role in mediating these specific interactions and that histone H1 and nuclear scaffold proteins may recognize a characteristic minor groove width or conformation. The effect of distamycin on these specific DNA-protein interactions in vitro suggests that binding of SARs to the nuclear scaffold and SAR-dependent nucleation of H1 assembly might be important targets of the drug in vivo.
Käs
E
E
Department of Molecular Biology, University of Geneva, Switzerland.
Izaurralde
E
E
Laemmli
U K
UK
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D002474:Cell-Free System; D002843:Chromatin / Q000648:ultrastructure*; D004247:DNA / Q000378:metabolism*; D004214:Distamycins / Q000494:pharmacology*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D009024:Morphogenesis; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*; D011067:Poly dA-dT / Q000378:metabolism*; D011089:Polydeoxyribonucleotides / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping
D002843:Chromatin; D004214:Distamycins; D006657:Histones; D009838:Oligodeoxyribonucleotides; D011089:Polydeoxyribonucleotides; D011758:Pyrroles; C016023:oligo(dA-dT); D011067:Poly dA-dT; D004247:DNA