The hormone-sensitive lipase gene is transcribed from at least five alternative first exons in mouse adipose tissue

Hormone-sensitive lipase (HSL) mediates triglyceride hydrolysis in adipocyt es, in which its expression varies with physiological stress and is control led posttranslationally and transcriptionally. We sequenced the mouse HSL g ene for 8.2 kb upstream of the translation start codon and studied the stea dy-state HSL mRNA levels in mouse adipose tissue. In 50 clones derived from primer extension and PCR of mouse adipose cDNA, we found five distinct 5' extremities that correspond to distinct exons in genomic DNA. Exon A is loc ated similar to7 kb 5' to the HSL translation start site. Exons B, C, and D are clustered 1.5-2 kb upstream, and the previously described exon 1 is im mediately upstream and contiguous with the previously described HSL transla tion start site. Exon A is located similar to7 kb upstream and contains an in-frame methionine codon that could potentially generate another HSL isofo rm with 43 additional N-terminal residues. cDNA clones containing the newly described exons suggested that each exon has several transcription start s ites but that all splice to an acceptor site located 20 nt upstream of the translation initiation codon in exon 1. HSL transcription in mouse adipose tissue originates from multiple sites in the 7-kb region between exon A and exon 1, with peaks at exon C (50-70% of HSL transcripts), exon 1 (5-30%), and exon A (similar to 10%). There are multiple potential transcription fac tor-binding elements upstream of each exon, suggesting the possibility of d ifferential transcriptional regulation of HSL in different tissues and unde r various physiologic conditions.