PuSH - Publikationsserver des Helmholtz Zentrums München

Lengler, J. ; Krausz, E. ; Tomarev, S.* ; Prescott, A.* ; Quinlan, R.A.* ; Graw, J.

Antagonistic action of Six3 and Prox1 at the ϒ-crystallin promoter.

Nucleic Acids Res. 29, 515-526 (2001)
Verlagsversion Volltext DOI
Open Access Gold
Creative Commons Lizenzvertrag
Gamma-crystallin genes are specifically expressed in the eye lens. Their promoters constitute excellent models to analyse tissue-specific gene expression. We investigated murine CRYGE/f promoters of different length in lens epithelial cell lines. The most active fragment extends from position -219 to +37. Computer analysis predicts homeodomain and paired-domain binding sites for all rodent CRYGD/e/f core promoters. As examples, we analysed the effects of Prox1 and Six3, which are considered important transcription factors involved in lens development. Because of endogenous Prox1 expression in N/N1003A cells, a weak stimulation of CRYGE/f promoter activity was found for PROX1. In contrast, PROX1 stimulated the CRYGF promoter 10-fold in CD5A cells without endogenous PROX1. In both cell lines Six3 repressed the CRYGF promoter to 10% of its basal activity. Our cell transfection experiments indicated that CRYG expression increases as Six3 expression decreases. Prox1 and Six3 act antagonistically on regulation of the CRYGD/e/f promoters. Functional assays using randomly mutated gammaF-crystallin promoter fragments define a Six3-responsive element between -101 and -123 and a Prox1-responsive element between -151 and -174. Since Prox1 and Six3 are present at the beginning of lens development, expression of CRYGD/e/f is predicted to remain low at this time. It increases as Six3 expression decreases during ongoing lens development.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter FIBER CELL-DIFFERENTIATION; LENS-SPECIFIC EXPRESSION; HOMEOBOX GENE PROX-1; TRANSCRIPTION FACTOR; EYE DEVELOPMENT; MURINE GAMMA-2-CRYSTALLIN; NUCLEOTIDE-SEQUENCE; REGULATORY ELEMENTS; IN-VITRO; MOUSE
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Quellenangaben Band: 29 , Heft: 2, Seiten: 515-526 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Begutachtungsstatus Peer reviewed