Organization, evolutionary conservation, expression and unusual Alu density of the human gene for pigment epithelium-derived factor, a unique neurotrophic serpin.
PEDF is a neurotrophic serpin that promotes a neuronal phenotype and augments neuronal cell survival. The isolation, sequence and structural analysis of the human PEDF gene and its promoter along with its evolutionary conservation and expression in human tissues are now described. The gene spans approximately 16 kb and is divided among 8 exons and 7 introns, the junctions of which conform to the AG/GT consensus rule. PEDF appears to fall into the ovalbumin/PAI-2 subgrouping of serpins and is structurally far different from GDN/PN-1, the only other neurotrophic serpin reported to date. The immediate 5'-flanking region is dominated by a dense cluster of Alu repeats in which are embedded several promoter consensus sequences. A CAAT box is present at -43. The putative promoter region is also far different from that reported for GDN/PN-1. Comparable hybridization signals of 23 kb EcoRI fragments containing the PEDF gene are observed by Southern blot analysis in all primate, mammal and avian species examined; conservation is particularly evident among the primates. Northern blot analysis confirms the presence of the PEDF transcript in a broad range of human fetal and adult tissues including almost all brain areas examined, underscoring differences with GDN/PN-1 which, in the adult brain, is only expressed in glia and a subset of neurons.
Tombran-Tink
J
J
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. jtink@helix.nih.gov
Mazuruk
K
K
Rodriguez
I R
IR
Chung
D
D
Linker
T
T
Englander
E
E
Chader
G J
GJ
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D001921:Brain / Q000378:metabolism; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors; D010053:Ovary / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D010802:Phylogeny; D010920:Placenta / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D015843:Serpins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D011506:Proteins; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor