Revised genomic organization of FBN1 and significance for regulated gene expression

FBN1 encodes fibrillin-1, an extracellular matrix protein that is defective in Marfan syndrome, This gene is divided into 65 exons and was previously re ported to be approximately 110 kb in length. The existence of 3 exons up stream of the exon containing the putative initiating methionine left open the possibility of alternative fibrillin-1 isoforms that vary at their N-te rmini. Detailed examination of YACs containing human FBN1 reveal that the g ene is 200 kb, almost twice as large as previously thought. Characterizatio n of the porcine FBN1 cDNA and 5' flanking sequence demonstrates extreme co nservation between the pig and the human predicted proteins and argues agai nst the possibility of alternative amino-terminal coding sequence. These da ta further our understanding of the regulatory requirements for gene expres sion and establish a framework for recombinant expression of fibrillin-1. ( C) 1999 Academic Press.