Characterization of the 5' regulatory region of the mouse angiopoietin-like protein 4.

The 5' regulatory region of the mouse angiopoietin-like protein 4 (mANGPTL4), a remarkably versatile secreted protein responsible for hyperlipidaemia and angiogenesis, was cloned and functionally characterized. Three potential transcriptional start sites were determined by 5'-RACE and found to be at -129, -126 and -118, relative to the translation initiation codon. The activities of the putative promoters were confirmed using a firefly luciferase reporter gene assay system, following transient transfection into COS-1 cells. The PPAR alpha-regulated region and the minimal region required for basal activity of the mANGPTL4 promoter were determined by generating a series of deletion constructs, and were found to be encoded by a sequence between -2761 to -383 and -50 to -30, relative to the transcription start site. Putative recognition sequences for the transcription factor AP2 were identified in the minimal promoter sequences. These results are the first molecular characterization of the regulatory region of this important gene.