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dc.contributor.authorTaylor, Alanen_US
dc.contributor.authorWebster, Keith A.en_US
dc.contributor.authorGustafson, Thomas A.en_US
dc.contributor.authorKedes, Larryen_US
dc.identifier.citationMolecular and cellular biochemistry. 1997 Apr; 169(1-2): 61-72.en_US
dc.descriptionClick on the DOI link below to access the article (may not be free).en_US
dc.description.abstractThe anticancer drug, distamycin A, alters DNA conformation by binding to A/T-rich domains. We propose that binding of the drug to DNA alters transcription factor interactions and that this may alter genetic regulation. We have analyzed the effects of distamycin A upon expression of the muscle-specific cardiac and skeletal alpha-actin genes which have A/T-rich regulatory elements in their promoters. Distamycin A specifically inhibited endogenous muscle genes in the myogenic C2 cell line and effectively eliminated the myogenic program. Conversely, when 10T1/2C18 derived pleuripotential TA1 cells were induced to differentiate in the presence of distamycin A, adipocyte differentiation was enhanced whereas the numbers of cells committing to the myogenic program decreased dramatically. Using the mobility shift assay distamycin A selectively inhibited binding of two important transcription factors, SRF and MEF2, to their respective A/T-rich elements. The binding of factors Sp1 and MyoD were not affected. The inhibition of factor binding correlated with a repression of muscle-specific promoter activity as assayed by transient transfection assays. Co-expression of the myoD gene, driven by a distamycin A-insensitive promoter, failed to relieve the inhibition of these muscle-specific promoters by distamycin A. Additionally, SRF and MEF2 dependent promoters were selectively down regulated by distamycin A. These results suggest that distamycin A may inhibit muscle-specific gene expression by selectively interfering with transcription factor interactions and demonstrate the importance of these A/T-rich elements in regulating differentiation of this specific cell type.en_US
dc.description.sponsorshipNHLBI NIH HHSen_US
dc.publisherSpringer New Yorken_US
dc.relation.ispartofseriesMolecular and cellular biochemistryen_US
dc.subjectResearch Support, Non-U.S. Gov'ten_US
dc.subjectResearch Support, U.S. Gov't, Non-P.H.S.en_US
dc.subjectResearch Support, U.S. Gov't, P.H.S.en_US
dc.subject.meshActins/drug effectsen_US
dc.subject.meshAntineoplastic Agents/pharmacologyen_US
dc.subject.meshCell Differentiation/drug effectsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshGene Expression/drug effectsen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshTranscription Factors/drug effectsen_US
dc.titleThe anti-cancer agent distamycin A displaces essential transcription factors and selectively inhibits myogenic differentiationen_US
dc.description.versionpeer revieweden_US
dc.rights.holderCopyright © 1997, Springer Netherlandsen_US

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