title: New insights into adipocyte-specific leptin gene expression.
abstract: The adipocyte-derived hormone leptin is a critical regulator of many physiological functions, ranging from satiety to immunity. Surprisingly, very little is known about the transcriptional pathways that regulate adipocyte-specific expression of leptin. In a recent published study, we pursued a strategy integrating BAC transgenic reporter mice, in vitro reporter assays, and chromatin state mapping to locate an adipocyte-specific cis-element upstream of theLEPgene in human fat cells. Quantitative proteomics (stable isotope labeling by amino acids in cell culture, SILAC) with affinity enrichment of protein-DNA complexes identified the transcription factor FOSL2 as a specific binder to the identified region. We confirmed that FOSL2 is an important regulator ofLEPgene expression in vitro and in vivo using cell culture models and genetic mouse models. In this commentary, we discuss the transcriptional regulation ofLEPgene expression, our strategy to identify an adipocyte-specific cis-regulatory element and the transcription factor(s) responsible forLEPgene expression. We also discuss our data on FOSL2 and leptin levels in physiology and pathophysiology. We speculate on unanswered questions and future directions.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism; Beth Israel Deaconess Medical Center; Boston, MA USA ; Dana-Farber Cancer Institute and Department of Cell Biology; Harvard Medical School; Boston, MA USA.
authors.forename: Christiane D
authors.initials: CD
authors.lastname: Wrann
authors.forename: Evan D
authors.initials: ED
authors.lastname: Rosen
keywords: ChIP-Seq; Fosl2; SILAC; adipose; diabetes; leptin; obesity; transcription