STRUCTURAL CHARACTERIZATION OF THE COMPLETE HUMAN PERLECAN GENE AND ITS PROMOTER

The complete intron-exon organization of the gene encoding human perle can (HSPG2), the major heparan sulfate proteoglycan of basement membra nes, has been elucidated, and specific exons have been assigned to cod ing sequences for the modular domains of the protein core. The gene wa s composed of 94 exons, spanning > 120 kbp of genomic DNA. The exon ar rangement was analyzed vis-a-vis the modular structure of the perlecan , which harbors protein domains homologous to the low density lipoprot ein receptor, laminin, epidermal growth factor, and neural cell adhesi on molecule. The exon size and the intron phases were highly conserved when compared to the corresponding domains of the homologous genes, s uggesting that most of this modular proteoglycan has evolved from a co mmon ancestor by gene duplication or exon shuffling. The 5' flanking r egion revealed a structural organization characteristic of housekeepin g and growth control-related genes. It lacked canonical TATA or CAAT b oxes, but it contained several GC boxes with binding sites for the tra nscription factors SP1 and ETF. Consistent with the lack of a TATA ele ment, the perlecan gene contained multiple transcription initiation si tes distributed over 80 bp of genomic DNA. These results offer insight s into the evolution of this chimeric molecule and provide the molecul ar basis for understanding the transcriptional control of this importa nt gene.