The LIM domain homeobox gene isl-1 is a positive regulator of glycoprotein alpha 2 (GPA2), a subunit of thyrostimulin.
Two glycoprotein hormone subunits, glycoprotein hormone subunit alpha (GPA) 2 and glycoprotein hormone subunit beta (GPB) 5, have recently been discovered. When expressed as recombinant proteins, they heterodimerize to form a novel thyrotrophic hormone, thyrostimulin. Recently, we have shown that GPA2 is expressed in both human pancreas and anterior pituitary. To explore the transcriptional regulation of GPA2, we identified from human pancreas full length RNA, the transcription start site (TSS) of the human GPA2 gene. A potential binding site for the LIM homeodomain transcription factor isl-1, which is closely associated with endocrine organs, was found at -2368 to -2363 bp upstream from TSS. The exogenously expressed isl-1 dose-dependently increased the GPA2 promoter activity up to two-fold in the AtT20 mouse corticotroph cell line. In chromatin immunoprecipitation assays we show the binding of isl-1 molecule to the predicted site. The reporter assay also showed that GPA2 transcription is unaffected by tri-iodothyronine or thyroid hormone receptor beta1 (TRbeta1), suggesting that the regulation of GPA2 might be different from the regulations of GSUalpha or TSHbeta, known as hypothalamus-pituitary-thyroid (HPT) axis. This study illustrated that human GPA2 is positively regulated by isl-1, suggesting that this protein associates with endocrine systems including the pituitary and pancreas.
Suzuki
Chizuko
C
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Japan.
Nagasaki
Hiroshi
H
Okajima
Yoshiki
Y
Suga
Hidetaka
H
Arima
Hiroshi
H
Iwasaki
Yasumasa
Y
Oiso
Yutaka
Y
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology
D006023:Glycoproteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; C458339:thyrostimulin; D014284:Triiodothyronine; D008156:Luciferases