The genomic organization of mouse resistin reveals major differences from the human resistin: functional implications.
The resistin gene is a potential candidate for the etiology of insulin resistance and type 2 diabetes and has been implicated as the molecular link between type 2 diabetes and obesity. Unlike the mouse resistin, expression of the human resistin appears to be regulated differently. We report comparative analyses of the mouse and human genomic fragments encoding the resistin gene. At the amino acid level the two proteins exhibit 59% identity. While at the mRNA level the human resistin shows 64.4% sequence identity with its mouse counterpart, the mouse resistin genomic sequence displays only 46.7% sequence identity with the human resistin and is almost three times bigger than the human resistin. The intronic sequences per se displayed the least identities (28.7%), however the intron boundaries were highly conserved between human and mouse. The mouse resistin carries a very large intron in the 3' UTR, which has a number of regulatory sequences possibly involved in differential gene expression. Of particular significance is the presence of a PPAR/RXR heterodimer binding site within intron X (IntX-PPRE) which may possibly confer TZD responsiveness. Oligonucleotides carrying the authentic PPAR/RXR binding element (Aco-PPRE) as well as IntX-PPRE specifically bound factors (PPAR/RXR heterodimers) present in differentiated 3T3-L1 adipocyte cells in an electrophoretic mobility shift assay. IntX-PPRE oligonucleotide modulated the expression of the luciferase reporter gene in transient transfection assays using 3T3-L1 cells.
Ghosh
Sudip
S
Molecular Biology Unit, National Institute of Nutrition, Jamia Osmania PO, Hyderabad 500007, India.
Singh
Anil K
AK
Aruna
Battu
B
Mukhopadhyay
Sangita
S
Ehtesham
Nasreen Z
NZ
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005796:Genes / Q000235:genetics; D006729:Hormones, Ectopic / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007438:Introns; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor; D011485:Protein Binding; D011506:Proteins; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D052243:Resistin; D017422:Sequence Analysis, DNA; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014162:Transfection
D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C499624:RETN protein, human; C486574:RETNLB protein, human; D011993:Recombinant Fusion Proteins; D052243:Resistin; C499623:Retn protein, mouse; C413576:Retnla protein, mouse; D013844:Thiazoles; D045162:Thiazolidinediones; D004247:DNA; D020932:Nerve Growth Factor; D008156:Luciferases; C039671:ciglitazone