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 reported to be approximately 110 kb in length. The existence of 3 exons upstream of the exon containing the putative initiating methionine left open the possibility of alternative fibrillin-1 isoforms that vary at their N-termini. Detailed examination of YACs containing human FBN1 reveal that the gene is 200 kb, almost twice as large as previously thought. Characterization of the porcine FBN1 cDNA and 5' flanking sequence demonstrates extreme conservation between the pig and the human predicted proteins and argues against the possibility of alternative amino-terminal coding sequence. These data further our understanding of the regulatory requirements for gene expression and establish a framework for recombinant expression of fibrillin-1.
Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA.
N J
NJ
Biery
Z A
ZA
Eldadah
C S
CS
Moore
G
G
Stetten
F
F
Spencer
H C
HC
Dietz
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D018244:Chromosomes, Artificial, Yeast; D005091:Exons; D000071838:Fibrillin-1; D000071837:Fibrillins; D005786:Gene Expression Regulation; D015698:Genomic Library; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D015183:Restriction Mapping; D016415:Sequence Alignment; D013552:Swine; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse