Mutually dependent response elements in the cis-regulatory region of the neurotensin/neuromedin N gene integrate environmental stimuli in PC12 cells
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Department of Molecular Genetics and Microbiology
Medical Subject Headings
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
Life Sciences | Medicine and Health Sciences
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.
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Citation: Neuron. 1990 May;4(5):783-95.
Kislauskis, Edward H. and Dobner, Paul R., "Mutually dependent response elements in the cis-regulatory region of the neurotensin/neuromedin N gene integrate environmental stimuli in PC12 cells" (1990). GSBS Student Publications. 609.