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Titolo:
Thyroid transcription factor 1 and Pax8 synergistically activate the promoter of the human thyroglobulin gene
Autore:
Espinoza, CR; Schmitt, TL; Loos, U;
Indirizzi:
Univ Ulm Klinikum, Dept Internal Med 1, D-89081 Ulm, Germany Univ Ulm Klinikum Ulm Germany D-89081 ternal Med 1, D-89081 Ulm, Germany
Titolo Testata:
JOURNAL OF MOLECULAR ENDOCRINOLOGY
fascicolo: 1, volume: 27, anno: 2001,
pagine: 59 - 67
SICI:
0952-5041(200108)27:1<59:TTF1AP>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-A GENE; PRODRUG THERAPY; SYMPORTER GENE; WILMS-TUMORS; FACTOR-I; EXPRESSION; TTF-1; UPSTREAM; IDENTIFICATION; CARCINOMA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Loos, U Univ Ulm Klinikum, Dept Internal Med 1, Robert Koch Str 8, D-89081Ulm, Germany Univ Ulm Klinikum Robert Koch Str 8 Ulm Germany D-89081 , Germany
Citazione:
C.R. Espinoza et al., "Thyroid transcription factor 1 and Pax8 synergistically activate the promoter of the human thyroglobulin gene", J MOL ENDOC, 27(1), 2001, pp. 59-67

Abstract

Thyroglobulin (Tg) is an essential thyroid-specific protein, which serves as the matrix for thyroid hormone biosynthesis. To obtain new insights in the regulation of Tg gene expression, we investigated the interaction of thehuman Tg promoter with the thyroid-specific transcription factors TTF-1 and Pax8. A reporter gene, containing a 202 bp fragment from the human Tg 5 '-flanking region including the promoter sequence and the transcriptional start site, and expression vectors containing the cDNAs for human TTF-1 and Pax8 were used in cotransfection experiments, in the non-thyroidal cell lines COS-7 and HeLa. Pax8 increased the specific transcriptional activity of the Tg promoter about threefold, whereas cotransfection with the homeodomain-containing protein TTF-1 stimulated promoter activity from six- to tenfold. The simultaneous expression of both factors stimulated the Tg promoter activity in a multiplicative manner up to 25-fold. TTF-1 binding sites couldbe localized precisely by lectron mobility shift assay. The two binding elements corresponded to sites A and C in the rat Tg promoter. Site-directed mutagenesis of three nucleotides in each binding element inhibited binding of TTF-1 to the two oligonucleotides. In cotransfection experiments, the mutant site C decreased TTF-1 transactivation to 26% of the wild-type, whereas an additional mutation in the site A reduced this value to almost zero, thus proving the physiological relevance of these sites. The present resultsdemonstrate that the activity of the human Tg promoter is closely dependent on the function of TTF-1 and Pax8, opening the field for further investigations of pathological alterations of Tg gene expression.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 07:42:25