The gene structure and minimal promoter of the human agouti related protein

The murine agouti related protein (mAGRP) is upregulated in obese and diabe tic mice and stimulates hyperphagia when administered intracerebroventricul arly (i.c.v.) or when overexpressed in transgenic mice. The human ortholog, hAGRP, has been isolated and has similar molecular and physiological prope rties. Here, we report the complete gene structure of the human AGRP gene a nd upstream regions with differential promoter activity. A polymorphism, A6 7T, in the third exon was identified but was not associated with obesity- o r type 2 diabetes-related phenotypes. Putative binding sites for transcript ion factors were identified in the promoter of the gene including recogniti on sites for the signal transducers and activators of transcription (STATs) that may potentially mediate leptin's action in the hypothalamus. The upst ream non-coding exon had significant promoter activity in a periphery- but not so in a hypothalamus-derived cell line, suggesting that it might contai n the minimal promoter required for expression of the short transcript of h AGRP in the periphery. (C) 2001 Elsevier Science B.V. All rights reserved.