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dc.contributor.authorTavares, Daniel Jorge
dc.contributor.authorTully, Keith
dc.contributor.authorDobner, Paul R.
dc.date2022-08-11T08:08:49.000
dc.date.accessioned2022-08-23T16:09:21Z
dc.date.available2022-08-23T16:09:21Z
dc.date.issued1999-10-09
dc.date.submitted2009-01-13
dc.identifier.citation<p>J Biol Chem. 1999 Oct 15;274(42):30066-79.</p>
dc.identifier.issn0021-9258 (Print)
dc.identifier.doi10.1074/jbc.274.42.30066
dc.identifier.pmid10514493
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32673
dc.description.abstractThe promoter region of the mouse high affinity neurotensin receptor (Ntr-1) gene was characterized, and sequences required for expression in neuroblastoma cell lines that express high affinity NT-binding sites were characterized. Me(2)SO-induced neuronal differentiation of N1E-115 neuroblastoma cells increased both the expression of the endogenous Ntr-1 gene and reporter genes driven by NTR-1 promoter sequences by 3-4-fold. Deletion analysis revealed that an 83-base pair promoter region containing the transcriptional start site is required for Me(2)SO activation. Detailed mutational analysis of this region revealed that a CACCC box and the central region of a large GC-rich palindrome are the crucial cis-regulatory elements required for Me(2)SO induction. The CACCC box is bound by at least one factor that is induced upon Me(2)SO treatment of N1E-115 cells. The Me(2)SO effect was found to be both selective and cell type-restricted. Basal expression in the neuroblastoma cell lines required a distinct set of sequences, including an Sp1-like sequence, and a sequence resembling an NGFI-A-binding site; however, a more distal 5' sequence was found to repress basal activity in N1E-115 cells. These results provide evidence that Ntr-1 gene regulation involves both positive and negative regulatory elements located in the 5'-flanking region and that Ntr-1 gene activation involves the coordinate activation or induction of several factors, including a CACCC box binding complex.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=10514493&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1074/jbc.274.42.30066
dc.subjectAnimals; Base Sequence; *Cell Differentiation; Cloning, Molecular; DNA; Dimethyl Sulfoxide; Gene Expression Regulation; Mice; Molecular Sequence Data; Neuroblastoma; Neurons; Promoter Regions (Genetics); Receptors, Neurotensin; Regulatory Sequences, Nucleic Acid; Sequence Homology, Nucleic Acid; Tumor Cells, Cultured
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleSequences required for induction of neurotensin receptor gene expression during neuronal differentiation of N1E-115 neuroblastoma cells
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume274
dc.source.issue42
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1232
dc.identifier.contextkey693142
html.description.abstract<p>The promoter region of the mouse high affinity neurotensin receptor (Ntr-1) gene was characterized, and sequences required for expression in neuroblastoma cell lines that express high affinity NT-binding sites were characterized. Me(2)SO-induced neuronal differentiation of N1E-115 neuroblastoma cells increased both the expression of the endogenous Ntr-1 gene and reporter genes driven by NTR-1 promoter sequences by 3-4-fold. Deletion analysis revealed that an 83-base pair promoter region containing the transcriptional start site is required for Me(2)SO activation. Detailed mutational analysis of this region revealed that a CACCC box and the central region of a large GC-rich palindrome are the crucial cis-regulatory elements required for Me(2)SO induction. The CACCC box is bound by at least one factor that is induced upon Me(2)SO treatment of N1E-115 cells. The Me(2)SO effect was found to be both selective and cell type-restricted. Basal expression in the neuroblastoma cell lines required a distinct set of sequences, including an Sp1-like sequence, and a sequence resembling an NGFI-A-binding site; however, a more distal 5' sequence was found to repress basal activity in N1E-115 cells. These results provide evidence that Ntr-1 gene regulation involves both positive and negative regulatory elements located in the 5'-flanking region and that Ntr-1 gene activation involves the coordinate activation or induction of several factors, including a CACCC box binding complex.</p>
dc.identifier.submissionpathgsbs_sp/1232
dc.contributor.departmentDepartment of Molecular Genetics and Microbiology
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages30066-79
dc.contributor.studentKeith Tully
dc.description.thesisprogramNeuroscience


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