Intra- and Intermolecular Triplex DNA Formation in the Murine c-myb Proto-Oncogene Promoter Are Inhibited by Mithramycin
Identifieur interne : 002370 ( Main/Exploration ); précédent : 002369; suivant : 002371Intra- and Intermolecular Triplex DNA Formation in the Murine c-myb Proto-Oncogene Promoter Are Inhibited by Mithramycin
Auteurs : Nadarajah Vigneswaran ; Jeyasakthy Thayaparan ; Judy Knops ; John Trent ; Vladimir Potaman ; Donald M. Miller ; Wolfgang ZachariasSource :
- Biological Chemistry [ 1431-6730 ] ; 2001.
English descriptors
- Teeft :
- Agarose, Antiparallel, Assay, Base triplets, Binding site, Binding sites, Biochemistry, Biol, Cell lines, Chem, Chemical probes, Chromosome, Cleavage, Consensus sequence, Distamycin, Distamycin binding, Dnase, Duplex, Duplex target, Ethidium bromide, Final structure, First dimension, Gene, Gene expression, Gene regulation, Groove, Hdna formation, Helix, Human gene, Human promoter, Immunofluorescence, Immunofluorescence staining, Individual topoisomers, Intermolecular, Intermolecular triplex formation, Interphase nuclei, Intramolecular, Intramolecular structure, Intramolecular triplex, Intramolecular triplex formation, Magnesium ions, Major groove, Metaphase, Metaphase chromosomes, Minor groove, Minor groove width, Mirkin, Mithramycin, Mithramycin binding, Mithramycin duplex, Mobility shift analysis, Mobility shift assays, Modeling, Mountz, Murine, Murine genes, Murine promoter, Murine promoter region, Nuclease, Nuclease sensitivity, Nuclease sensitivity assays, Nucleic acids, Oncogene, Other hand, Plasmid, Plasmid pmyb, Plasmids pmyb, Pmyb, Previous study, Promoter, Promoter region, Promoter sequence, Puc8 vector, Sinden, Structural transition, Supercoiled, Supercoiled band, Target duplex, Target sequence, Third strand, Topoisomers, Transcription, Transcription elongation, Transcription factor, Transcription initiation site, Transcriptional, Transcriptional activity, Transition region, Triple helix, Triplex, Triplex formation, Triplex model, Triplex structure, Vigneswaran, Zacharias.
Abstract
Mithramycin inhibits transcription by binding to G/Crich sequences, thereby preventing regulatory protein binding. However, it is also possible that mithramycin inhibits gene expression by preventing intramolecular triplex DNA assembly. We tested this hypothesis using the DNA triplex adopted by the murine cmyb protooncogene. The 5regulatory region of cmyb contains two polypurine:polypyrimidine tracts with imperfect mirror symmetry, which are highly conserved in the murine and human cmyb sequences. The DNA binding drugs mithramycin and distamycin bind to one of these regions as determined by DNase I protection assay. Gel mobility shift assays, nuclease and chemical hypersensitivity and 2Dgel topological analyses as well as triplexspecific antibody binding studies confirmed the formation of purine*purine:pyrimidine inter and pyrimidine*purine:pyrimidine intramolecular triplex structures in this sequence. Mithramycin binding within the triplex target site displaces the major groovebound oligonucleotide, and also abrogates the supercoildependent HDNA formation, whereas distamycin binding had no such effects. Molecular modeling studies further support these observations. Triplexspecific antibody staining of cells pretreated with mithramycin demonstrates a reversal of chromosomal triplex structures compared to the nontreated and distamycintreated cells. These observations suggest that DNA minor groovebinding drugs interfere with gene expression by precluding intramolecular triplex formation, as well as by physically preventing regulatory protein binding.
Url:
DOI: 10.1515/BC.2001.040
Affiliations:
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Miller</name></author><author><name sortKey="Zacharias, Wolfgang" sort="Zacharias, Wolfgang" uniqKey="Zacharias W" first="Wolfgang" last="Zacharias">Wolfgang Zacharias</name></author></analytic><monogr></monogr><series><title level="j" type="abbrev">Biological Chemistry</title><idno type="ISSN">1431-6730</idno><imprint><publisher>Walter de Gruyter</publisher><date>2001</date><date type="e-published">2005</date><biblScope unit="vol">382</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="329">329</biblScope><biblScope unit="page" to="342">342</biblScope></imprint><idno type="ISSN">1431-6730</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1431-6730</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Agarose</term><term>Antiparallel</term><term>Assay</term><term>Base triplets</term><term>Binding site</term><term>Binding sites</term><term>Biochemistry</term><term>Biol</term><term>Cell lines</term><term>Chem</term><term>Chemical probes</term><term>Chromosome</term><term>Cleavage</term><term>Consensus sequence</term><term>Distamycin</term><term>Distamycin binding</term><term>Dnase</term><term>Duplex</term><term>Duplex target</term><term>Ethidium bromide</term><term>Final structure</term><term>First dimension</term><term>Gene</term><term>Gene expression</term><term>Gene regulation</term><term>Groove</term><term>Hdna formation</term><term>Helix</term><term>Human gene</term><term>Human promoter</term><term>Immunofluorescence</term><term>Immunofluorescence staining</term><term>Individual topoisomers</term><term>Intermolecular</term><term>Intermolecular triplex formation</term><term>Interphase nuclei</term><term>Intramolecular</term><term>Intramolecular structure</term><term>Intramolecular triplex</term><term>Intramolecular triplex formation</term><term>Magnesium ions</term><term>Major groove</term><term>Metaphase</term><term>Metaphase chromosomes</term><term>Minor groove</term><term>Minor groove width</term><term>Mirkin</term><term>Mithramycin</term><term>Mithramycin binding</term><term>Mithramycin duplex</term><term>Mobility shift analysis</term><term>Mobility shift assays</term><term>Modeling</term><term>Mountz</term><term>Murine</term><term>Murine genes</term><term>Murine promoter</term><term>Murine promoter region</term><term>Nuclease</term><term>Nuclease sensitivity</term><term>Nuclease sensitivity assays</term><term>Nucleic acids</term><term>Oncogene</term><term>Other hand</term><term>Plasmid</term><term>Plasmid pmyb</term><term>Plasmids pmyb</term><term>Pmyb</term><term>Previous study</term><term>Promoter</term><term>Promoter region</term><term>Promoter sequence</term><term>Puc8 vector</term><term>Sinden</term><term>Structural transition</term><term>Supercoiled</term><term>Supercoiled band</term><term>Target duplex</term><term>Target sequence</term><term>Third strand</term><term>Topoisomers</term><term>Transcription</term><term>Transcription elongation</term><term>Transcription factor</term><term>Transcription initiation site</term><term>Transcriptional</term><term>Transcriptional activity</term><term>Transition region</term><term>Triple helix</term><term>Triplex</term><term>Triplex formation</term><term>Triplex model</term><term>Triplex structure</term><term>Vigneswaran</term><term>Zacharias</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mithramycin inhibits transcription by binding to G/Crich sequences, thereby preventing regulatory protein binding. However, it is also possible that mithramycin inhibits gene expression by preventing intramolecular triplex DNA assembly. We tested this hypothesis using the DNA triplex adopted by the murine cmyb protooncogene. The 5regulatory region of cmyb contains two polypurine:polypyrimidine tracts with imperfect mirror symmetry, which are highly conserved in the murine and human cmyb sequences. The DNA binding drugs mithramycin and distamycin bind to one of these regions as determined by DNase I protection assay. Gel mobility shift assays, nuclease and chemical hypersensitivity and 2Dgel topological analyses as well as triplexspecific antibody binding studies confirmed the formation of purine*purine:pyrimidine inter and pyrimidine*purine:pyrimidine intramolecular triplex structures in this sequence. Mithramycin binding within the triplex target site displaces the major groovebound oligonucleotide, and also abrogates the supercoildependent HDNA formation, whereas distamycin binding had no such effects. Molecular modeling studies further support these observations. Triplexspecific antibody staining of cells pretreated with mithramycin demonstrates a reversal of chromosomal triplex structures compared to the nontreated and distamycintreated cells. These observations suggest that DNA minor groovebinding drugs interfere with gene expression by precluding intramolecular triplex formation, as well as by physically preventing regulatory protein binding.</div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Knops, Judy" sort="Knops, Judy" uniqKey="Knops J" first="Judy" last="Knops">Judy Knops</name><name sortKey="Miller, Donald M" sort="Miller, Donald M" uniqKey="Miller D" first="Donald M." last="Miller">Donald M. Miller</name><name sortKey="Potaman, Vladimir" sort="Potaman, Vladimir" uniqKey="Potaman V" first="Vladimir" last="Potaman">Vladimir Potaman</name><name sortKey="Thayaparan, Jeyasakthy" sort="Thayaparan, Jeyasakthy" uniqKey="Thayaparan J" first="Jeyasakthy" last="Thayaparan">Jeyasakthy Thayaparan</name><name sortKey="Trent, John" sort="Trent, John" uniqKey="Trent J" first="John" last="Trent">John Trent</name><name sortKey="Vigneswaran, Nadarajah" sort="Vigneswaran, Nadarajah" uniqKey="Vigneswaran N" first="Nadarajah" last="Vigneswaran">Nadarajah Vigneswaran</name><name sortKey="Zacharias, Wolfgang" sort="Zacharias, Wolfgang" uniqKey="Zacharias W" first="Wolfgang" last="Zacharias">Wolfgang Zacharias</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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