Mutually dependent response elements in the cis-regulatory region of the neurotensin/neuromedin N gene integrate environmental stimuli in PC12 cells
dc.contributor.author | Kislauskis, Edward H. | |
dc.contributor.author | Dobner, Paul R. | |
dc.date | 2022-08-11T08:08:59.000 | |
dc.date.accessioned | 2022-08-23T16:14:50Z | |
dc.date.available | 2022-08-23T16:14:50Z | |
dc.date.issued | 1990-05-01 | |
dc.date.submitted | 2008-10-15 | |
dc.identifier.citation | <p>Neuron. 1990 May;4(5):783-95.</p> | |
dc.identifier.issn | 0896-6273 (Print) | |
dc.identifier.doi | 10.1016/0896-6273(90)90205-T | |
dc.identifier.pmid | 2344411 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/33955 | |
dc.description.abstract | The expression of the gene encoding the neuroendocrine peptides neurotensin (NT) and neuromedin N is strictly dependent on simultaneous exposure to multiple inducers in PC12 pheochromocytoma cells. NT peptide and NT/N mRNA levels are synergistically induced by combinations of NGF, dexamethasone, activators of adenylate cyclase, and lithium ion. We have used transient transfection assays to delineate the rat NT/N gene sequences necessary for this complex regulation. Progressive deletions of the 5' flanking region revealed that sequences between -216 and +56 are sufficient to confer the full spectrum of responses exhibited by the endogenous gene to a reporter gene. Detailed mutational analysis of this region indicates that it is composed of an array of inducible cis-regulatory sequences, including AP-1, cAMP response, and glucocorticoid response elements. Specific mutation of either the AP-1 site or each of two cAMP response elements indicates that they are functionally interdependent. This array of response elements serves to integrate multiple environmental stimuli into a unified transcriptional response. | |
dc.language.iso | en_US | |
dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2344411&dopt=Abstract">Link to article in PubMed</a></p> | |
dc.relation.url | https://doi.org/10.1016/0896-6273(90)90205-T | |
dc.subject | Adrenal Gland Neoplasms; Amino Acid Sequence; Animals; Base Sequence; Chromosome Mapping; Fibroblasts; Gene Expression; Genes, Regulator; Molecular Sequence Data; Neurotensin; Peptide Fragments; Phenotype; Pheochromocytoma; Pituitary Gland; Promoter Regions (Genetics); Rats; Tumor Cells, Cultured | |
dc.subject | Life Sciences | |
dc.subject | Medicine and Health Sciences | |
dc.title | Mutually dependent response elements in the cis-regulatory region of the neurotensin/neuromedin N gene integrate environmental stimuli in PC12 cells | |
dc.type | Journal Article | |
dc.source.journaltitle | Neuron | |
dc.source.volume | 4 | |
dc.source.issue | 5 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/gsbs_sp/609 | |
dc.identifier.contextkey | 651079 | |
html.description.abstract | <p>The expression of the gene encoding the neuroendocrine peptides neurotensin (NT) and neuromedin N is strictly dependent on simultaneous exposure to multiple inducers in PC12 pheochromocytoma cells. NT peptide and NT/N mRNA levels are synergistically induced by combinations of NGF, dexamethasone, activators of adenylate cyclase, and lithium ion. We have used transient transfection assays to delineate the rat NT/N gene sequences necessary for this complex regulation. Progressive deletions of the 5' flanking region revealed that sequences between -216 and +56 are sufficient to confer the full spectrum of responses exhibited by the endogenous gene to a reporter gene. Detailed mutational analysis of this region indicates that it is composed of an array of inducible cis-regulatory sequences, including AP-1, cAMP response, and glucocorticoid response elements. Specific mutation of either the AP-1 site or each of two cAMP response elements indicates that they are functionally interdependent. This array of response elements serves to integrate multiple environmental stimuli into a unified transcriptional response.</p> | |
dc.identifier.submissionpath | gsbs_sp/609 | |
dc.contributor.department | Department of Molecular Genetics and Microbiology | |
dc.contributor.department | Graduate School of Biomedical Sciences | |
dc.source.pages | 783-95 |