The polypyrimidine/polypurine motif in the mouse mu opioid receptor gene promoter is a supercoiling-regulatory element
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UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2011-11-16Keywords
AnimalsBinding Sites
Camptothecin
Cell Line, Tumor
DNA
Gene Expression Regulation
Humans
Luciferases
Mice
Microscopy, Atomic Force
Nucleic Acid Conformation
Promoter Regions, Genetic
Purine Nucleotides
Pyrimidine Nucleotides
Receptors, Opioid, mu
Regulatory Sequences, Nucleic Acid
Reverse Transcriptase Polymerase Chain Reaction
Spectrum Analysis, Raman
Topoisomerase I Inhibitors
Cell Biology
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Show full item recordAbstract
The mu opioid receptor (MOR) is the principle molecular target of opioid analgesics. The polypyrimidine/polypurine (PPy/u) motif enhances the activity of the MOR gene promoter by adopting a non-B DNA conformation. Here, we report that the PPy/u motif regulates the processivity of torsional stress, which is important for endogenous MOR gene expression. Analysis by topoisomerase assays, S1 nuclease digests, and atomic force microscopy showed that, unlike homologous PPy/u motifs, the position- and orientation-induced structural strains to the mouse PPy/u element affect its ability to perturb the relaxation activity of topoisomerase, resulting in polypurine strand-nicked and catenated DNA conformations. Raman spectrum microscopy confirmed that mouse PPy/u containing-plasmid DNA molecules under the different structural strains have a different configuration of ring bases as well as altered Hoogsteen hydrogen bonds. The mouse MOR PPy/u motif drives reporter gene expression fortyfold more effectively in the sense orientation than in the antisense orientation. Furthermore, mouse neuronal cells activate MOR gene expression in response to the perturbations of topology by topoisomerase inhibitors, whereas human cells do not. These results suggest that, interestingly among homologous PPy/u motifs, the mouse MOR PPy/u motif dynamically responds to torsional stress and consequently regulates MOR gene expression in vivo.Source
Gene. 2011 Nov 1;487(1):52-61. Epub 2011 Jul 31. Link to article on publisher's siteDOI
10.1016/j.gene.2011.07.026Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49589PubMed ID
21839154Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.gene.2011.07.026