IDENTIFICATION OF A PLACENTAL ENHANCER FOR THE HUMAN LEPTIN GENE

Leptin is a hormone that regulates metabolic efficiency, energy expend iture, and food intake. Leptin is produced chiefly in adipose cells, b ut in humans, mRNA encoding leptin is also present in the placenta. He re we elucidate the basis for placental leptin production. The same pr omoter is used for adipose and placental transcription. An upstream en hancer functions in the JEG-3 and JAR choriocarcinoma cell lines but n ot in adipocytes or HeLa cells. The minimal positive acting region is 60 base pairs in length. This region is within a MER11 repetitive elem ent, suggesting that human placental expression of leptin is the resul t of insertion of this element. Binding analyses demonstrated three pr otein binding sites, designated placental leptin enhancer elements (PL E)1, PLE2, and PLE3. PLE2 binds Sp1. Enhancer activity was reduced by mutation of the PLE1 or PLE3 sites but was unaffected by alteration of PLE2. Proteins binding to PLE3 were present in JEG-3 and human placen tal nuclear extracts but not in extracts from non-placental sources. U pon triplication, the PLE3 element was a strong enhancer in choriocarc inoma cells but not in HeLa cells. The protein binding to the PLE3 mot if appears to be a novel, placenta-specific transcription factor.