ISSN:
0730-2312
Schlagwort(e):
pro-opiomelanocortin
;
DNA binding site
;
glucocorticoid-inhibitory element
;
Life and Medical Sciences
;
Cell & Developmental Biology
Quelle:
Wiley InterScience Backfile Collection 1832-2000
Thema:
Biologie
,
Chemie und Pharmazie
,
Medizin
Notizen:
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.
Zusätzliches Material:
6 Ill.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1002/jcb.240350404
