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Titolo:
Pit-1 binding sites at the somatotrope-specific DNase I hypersensitive sites I, II of the human growth hormone locus control region are essential forin vivo hGH-N gene activation
Autore:
Shewchuk, BM; Asa, SL; Cooke, NE; Liebhaber, SA;
Indirizzi:
Univ Penn, Dept Genet, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 ept Genet, Philadelphia, PA 19104 USA Univ Penn, Dept Med, Philadelphia, PA 19104 USA Univ Penn Philadelphia PAUSA 19104 Dept Med, Philadelphia, PA 19104 USA Univ Penn, Howard Hughes Med Inst, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Med Inst, Philadelphia, PA 19104 USA Univ Toronto, Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada Univ Toronto Toronto ON Canada M5G 1X5 b Med, Toronto, ON M5G 1X5, Canada
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 50, volume: 274, anno: 1999,
pagine: 35725 - 35733
SICI:
0021-9258(199912)274:50<35725:PBSATS>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-GLOBIN GENE; POSITION-EFFECT VARIEGATION; TRANS-ACTING FACTOR; TRANSCRIPTIONAL ACTIVATION; CHORIONIC SOMATOMAMMOTROPIN; PHYSICAL LINKAGE; CELL PHENOTYPES; EXPRESSION; MICE; DOMAIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Liebhaber, SA Univ Penn, Dept Genet, 415 Curie Blvd,428 Clin Res Bldg, Philadelphia, PA 19104 USA Univ Penn 415 Curie Blvd,428 Clin Res Bldg Philadelphia PA USA 19104
Citazione:
B.M. Shewchuk et al., "Pit-1 binding sites at the somatotrope-specific DNase I hypersensitive sites I, II of the human growth hormone locus control region are essential forin vivo hGH-N gene activation", J BIOL CHEM, 274(50), 1999, pp. 35725-35733

Abstract

The human growth hormone gene cluster is composed of five closely related genes. The 5'-most gene in the cluster, hGH-N, is expressed exclusively in somatotropes and lactosomatotropes of the anterior pituitary, Although the hGH-N promoter contains functional binding sites for multiple transcriptionfactors, including Spl, Zn-15, and Pit-1, predictable and developmentally appropriate expression of hGH-N transgenes in the mouse pituitary requires the presence of a previously characterized locus control region (LCR) composed of multiple chromatin DNase I hypersensitive sites (HS), LCR determinant(s) necessary for hGH-N transgene activation are largely conferred by two closely spaced HS (HS I,II) located 14.5 kilobase pairs upstream of the hGH-N gene. The region sufficient to mediate this activity has recently been sublocalized to a 404-base pair segment of HS I,II (F14 segment). In the present study, we identified multiple binding sites for the pituitary POU domain transcription factor Pit-1 within this segment. Using a transgenic founder assay, these sites were shown to be required for high level, position-independent, and somatotrope-specific expression of a linked hGH-N transgene,Because the Pit-1 sites in the hGH-N gene promoter are insufficient for such gene activation in vivo, these data suggested a unique chromatin-mediated developmental role for Pit-1 in the hGH LCR.

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Documento generato il 01/12/20 alle ore 16:24:55