Leptin is a fat hormone regulating energy homeostasis. Here, it is reported that the promoter and CpG island of the autosomal gene Leptin (LEP) is a tissue-specific differentially methylated region (T-DMR) and subject to dynamic methylation in human and mouse in vivo. Highly variable densities of cytosine methylation were detected by hairpin-bisulfite PCR among cells in human adipose tissue and peripheral blood leukocytes. Intermediate and low levels of methylation characterize the majority of human LEP epialleles. Low-density epialleles are often methylated at a specific CG site within the binding element of the C/EBP-alpha transcription factor. In the human LEP promoter, the methylation frequency at that site is 1.8-fold as great as the average frequency for all other CG sites analyzed. The Lep promoter has a significantly higher methylation density in mouse somatic tissues than in the human LEP promoter. Though the LEP CpG island is generally unmethylated in both human and mouse sperm, depletion of CG sites within the mouse promoter indicates occasional presence of methylated Lep epialleles in the germline. These findings suggest that LEP promoter methylation is normally imposed during postzygotic development, and that this epigenetic mark may play a role in modulating expression of an important metabolic gene.
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