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The adipocyte specific transcription factor C/EBPalpha modulates human ob gene expression
S G Miller1, P De Vos, M Guerre-Millo
1Ligand Pharmaceuticals, Inc., San Diego, CA 92121, USA.
Summary
The human ob gene, which produces leptin to regulate body weight, has been structurally analyzed. Its promoter requires only 217 bp for adipose tissue-specific expression, influenced by C/EBPalpha.
Area of Science:
- Genetics
- Molecular Biology
- Endocrinology
Background:
- Leptin (ob gene product) is a key signaling factor for body weight homeostasis.
- Ob gene expression is hormonally regulated and increased in obesity.
- Factors affecting human ob gene expression remain largely unknown.
Purpose of the Study:
- To describe the structure of the human ob gene.
- To analyze the functional elements of the human ob gene promoter.
- To investigate factors regulating human ob gene expression.
Main Methods:
- Genomic DNA cloning and characterization of the human ob gene.
- Functional analysis of the ob gene promoter using reporter assays.
- Site-directed mutagenesis to study transcription factor binding sites.
Main Results:
- The human ob gene comprises three exons spanning approximately 15 kb.
- A 217 bp region of the 5' sequence is sufficient for basal and C/EBPalpha-enhanced adipose tissue-specific expression.
- A single C/EBPalpha binding site within this region is crucial for inducibility.
Conclusions:
- The characterized human ob gene structure aids in studying obesity-related mutations.
- Understanding ob gene regulation is vital for obesity prevention and treatment.
- C/EBPalpha plays a significant role in regulating human ob gene expression.