Sequence-Specific Minor Groove Binding Ligands as Potential Regulators of Gene Expression in Xenopus Laevis Oocytes
| Autor: | G. V. Gursky, S. L. Grokhovsky, Sergey Belikov, Maria G. Isaguliants, A. N. Surovaya |
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| Rok vydání: | 2005 |
| Předmět: |
Transcriptional Activation
Molecular Sequence Data DNA Footprinting Xenopus Ligands Xenopus laevis chemistry.chemical_compound Glucocorticoid receptor Structural Biology Sequence Homology Nucleic Acid Gene expression Animals Deoxyribonuclease I Binding site Promoter Regions Genetic Molecular Biology Regulation of gene expression Binding Sites Base Sequence biology Mouse mammary tumor virus DNase-I Footprinting Netropsin General Medicine biology.organism_classification Molecular biology Cell biology Gene Expression Regulation Mammary Tumor Virus Mouse chemistry Oocytes Female |
| Zdroj: | Karolinska Institutet |
| ISSN: | 1538-0254 0739-1102 |
| Popis: | The mouse mammary tumor virus (MMTV) promoter is induced by glucocorticoid hormone. A robust hormone- and receptor-dependent gene activation could be reproduced in Xenopus laevis oocytes. The homogeneous response in this system allowed a detailed analysis of the DNA-protein interactions following hormone activation. The strategy of artificial regulating of gene activity by sequence-specific minor groove binding ligands is very attractive. We have synthesized and studied the interaction with DNA of bis-linked netropsin derivatives in which two monomers are attached via short linkers in head-to-head and tail-to-tail manners. We have found that cis-diammine-platinum bridged bis-netropsin added to Xenopus oocytes media penetrates cellular and nuclear membrane and binds selectively to the MMTV promoter at the DNA segment that partly overlaps with the site recognized by glucocorticoid receptor. DNase I footprinting studies demonstrate that there are more stronger binding sites for cis-diammine-platinum bridged bis-netropsin on the naked MMTV DNA which are found to be inaccessible for its binding in oocytes. |
| Databáze: | OpenAIRE |
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