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Titolo:
An element in intron 1 of the CFTR gene augments intestinal expression in vivo
Autore:
Rowntree, RK; Vassaux, G; McDowell, TL; Howe, S; McGuigan, A; Phylactides, M; Huxley, C; Harris, A;
Indirizzi:
Univ Oxford, John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DS, England Univ Oxford Oxford England OX3 9DS Inst Mol Med, Oxford OX3 9DS, England Univ London Imperial Coll Sci Technol & Med, Div Biomed Sci, Sect Cell & Mol Biol, London SW7 2AZ, England Univ London Imperial Coll Sci Technol & Med London England SW7 2AZ gland
Titolo Testata:
HUMAN MOLECULAR GENETICS
fascicolo: 14, volume: 10, anno: 2001,
pagine: 1455 - 1464
SICI:
0964-6906(20010701)10:14<1455:AEII1O>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS GENE; I-HYPERSENSITIVE SITES; YEAST ARTIFICIAL CHROMOSOME; TISSUE-SPECIFIC EXPRESSION; PROMOTER REGION; MESSENGER-RNA; CELL LINE; IDENTIFICATION; DNA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Harris, A Univ Oxford, John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DS, England Univ Oxford Oxford England OX3 9DS ed, Oxford OX3 9DS, England
Citazione:
R.K. Rowntree et al., "An element in intron 1 of the CFTR gene augments intestinal expression in vivo", HUM MOL GEN, 10(14), 2001, pp. 1455-1464

Abstract

The elements controlling the complex developmental and tissue-specific expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene lie outside the basal promoter region and have not been characterized. We previously identified a tissue-specific DNase I hypersensitive site (DHS) in intron 1 (185 + 10 kb) of the CFTR gene. Here we show that removal of the core element abolishes the activity of this DHS in transient transfection assays of reporter/enhancer gene constructs. We then compared expressionfrom a 310 kb yeast artificial chromosome (YAC) that contains the entire CFTR gene with expression from the same YAC from which the DHS element had been deleted. Stable transfection of a human colon carcinoma cell line showed that transcription from the deleted YAC was reduced by similar to 60%. Intransgenic mice, deletion of the intron 1 DHS had no effect on expression in the lung, but reduced expression in the intestine by similar to 60%. Thus, the regulatory element associated with the intron 1 DHS is tissue-specific and is required for normal CFTR expression levels in the intestinal epithelium in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 06:39:55