Characterization of the structural gene and putative 5′-regulatory sequences for human proopiomelanocortin

• Published in: Nature (London) 1982-05, Vol.297 (5864), p.335-339
• Main Authors: Cochet, Madeleine, Chang, Annie C. Y, Cohen, Stanley N
• Format: Article
• Language: English
• Subjects: Base Sequence; Binding Sites; Gene Expression Regulation - drug effects; Genes; Genes, Regulator; Glucocorticoids - pharmacology; Humanities and Social Sciences; Humans; letter; multidisciplinary; Operon; Pituitary Hormones, Anterior - genetics; Pro-Opiomelanocortin; Protein Precursors - genetics; Receptors, Glucocorticoid - metabolism; Science; Science (multidisciplinary)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/297335a0

It is now well established that the hormones corticotropin (ACTH) and β -lipotropin ( β -LPH) are contained within a common precursor peptide called proopiomelanocortin (POMC), which is synthesized in the anterior and/or intermediate lobes of the pituitary 1–3 and in the hypothalamus 4 . The recent cloning of a ‘full-size’ cDNA copy of bovine POMC mRNA has revealed the presence of additional peptides in the previously ‘cryptic’ segment of the precursor protein 5 . This cDNA has been used as a hybridization probe for the isolation and characterization of a bovine genomic DNA segment encoding the complete POMC mRNA 6 , and for isolation of part of the corresponding human genomic DNA sequence 7 . DNA sequence analysis of these isolates and of part of the rat POMC gene 8 has shown that, in the species studied, certain segments of the POMC structural gene have been conserved during evolution, whereas the nucleotide sequences of other segments have diverged sharply. We have now isolated and characterized a 11.6-kilobase (kb) human genomic DNA fragment that encodes the complete POMC mRNA and putative regulatory sequences proximate to the gene (which is repressed by glucocorticoids in vivo 9 ). We have also analysed the 800-base pair (bp) segment preceding the mRNA coding sequence, within which—at a position nearly 480 bp upstream from the mRNA start site—is a 21-bp segment that shares homology with a DNA sequence beginning 370 bp upstream from two other glucocorticoid-controlled genes. We speculate that these sequences may be involved in the regulation of POMC gene expression by glucocorticoids.