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The pro-opiomelanocortin gene is widely expressed in human tissues, although both transcriptional initiation sites and regulation appear to be tissue specific. In order to determine how promoter and enhancer choice is effected, we have studied the methylation pattern of the gene in a number of normal tissues, tumours and cell lines. Variability of this pattern was observed in the 5'-flanking DNA, particularly at the HpaII site located at –304 bp upstream from the pituitary CAP site. This site was generally methylated in tissues likely to express the predominant extrapituitary (800 nucleotide) message, while in tissues known to express the normal pituitary (1150 nucleotide) message and longer species, a tendency towards undermethylation was observed. Although the sites at which variable methylation occurs did not correspond to established binding sites for regulatory proteins, many of these regions remain to be determined and thus it is possible that methylation may be influential in the tissue-specific regulation of this gene.

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				J. Newell-Price, P. King, and A. J. L. Clark The CpG Island Promoter of the Human Proopiomelanocortin Gene Is Methylated in Nonexpressing Normal Tissue and Tumors and Represses Expression Mol. Endocrinol., February 1, 2001; 15(2): 338 - 348. [Abstract] [Full Text]