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Pro‐opiomelanocortin gene: A model for negative regulation of transcription by glucocorticoids
Author(s) -
Drouin Jacques,
Charron Jean,
Gagner JeanPierre,
Jeannotte Lucie,
Nemer Mona,
Plante Richard K.,
Wrange Örjan
Publication year - 1987
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240350404
Subject(s) - glucocorticoid receptor , biology , promoter , anterior pituitary , transcription (linguistics) , gene , transcription factor , glucocorticoid , microbiology and biotechnology , response element , hormone response element , gene expression , genetics , endocrinology , hormone , linguistics , philosophy , breast cancer , cancer , estrogen receptor
The gene encoding pro‐opiomelanocortin (POMC) offers an interesting model system to study negative control of transcription in eucaryotes. Indeed, glucocorticoid hormones specifically inhibit transcription of the POMC gene in the anterior pituitary. The POMC gene is predominantly expressed in the anterior and intermediate lobes of the pituitary. However, only anterior pituitary POMC transcription is inhibited by glucocorticoids and stimulated by corticotropino‐releasing hormone (CRH). Rat POMC promoter sequences required for anterior pituitary‐specific expression were localized between positions −480 and −34 base pairs (bp) by DNA‐mediated gene transfer into the POMC‐expressing tumor cells, AtT‐20. These POMC promoter sequences also confer glucocorticoid inhibition of transcription. While two of the six in vitro binding sites for purified glucocorticoid receptor identified in the rat POMC gene are within these sequences, only one is required for glucocorticoid inhibition; this binding site is located at position −63 bp in the promoter and overlaps a putative CCA AT box sequence. The DNA sequence of the POMC −63 bp receptor binding site is homologous to receptor binding sites identified in the glucocorticoid responsive element (GRE) of glucocorticoid‐inducible genes. However, DNA sequence divergencies between these sites, in particular within the conserved hexanucleotide sequence 5′‐TGTYCT‐3′, may be involved in their opposite transcriptional activity. Alternatively, binding of the receptor in the promoter proximal region of the POMC gene may inhibit transcription by a hormone‐dependent represser mechanism.