Cloning and characterization of the 5(')-flanking region of the human ghrelin gene.

Ghrelin, a novel growth hormone releasing peptide, was recently isolated from stomach. We have cloned and characterized the 5(')-flanking region, containing from -2000 to -1 upstream from the translation start site of the human ghrelin gene. There was neither typical GC nor CAAT box but there were a TATATAA element and putative binding sites for several transcription factors. Ghrelin promoter was activated only in human stomach derived ECC10 cells among several cell lines examined. Functional analysis showed that promoter activity was increased by deletion of nucleotides from -2000 to -605 whereas it was decreased by further deletion and that the TATATAA element is not functioning. Glucagon and its second messenger cAMP enhanced the promoter activity, suggesting that stimulated transcription of ghrelin gene by glucagon might be responsible for increased ghrelin production during fasting at least in part. These initial characterizations will facilitate further studies of the regulatory mechanisms for ghrelin gene expression.