Antagonistic action of Six3 and Prox1 at the γ-crystallin promoter

Johannes Lengler, Eberhard Krausz, Stanislav Tomarev, Alan Prescott, Roy A. Quinlan, Jochen Graw (Lead / Corresponding author)

Research output: Contribution to journalArticle

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Abstract

γ-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 Crygelf 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 γF-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.

Original languageEnglish
Pages (from-to)515-526
Number of pages12
JournalNucleic Acids Research
Volume29
Issue number2
DOIs
Publication statusPublished - 15 Jan 2001

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Crystallins
Lenses
Cell Line
Crystalline Lens
Transfection
Rodentia
Transcription Factors
Epithelial Cells
Binding Sites
Gene Expression
Genes

Cite this

Lengler, J., Krausz, E., Tomarev, S., Prescott, A., Quinlan, R. A., & Graw, J. (2001). Antagonistic action of Six3 and Prox1 at the γ-crystallin promoter. Nucleic Acids Research, 29(2), 515-526. https://doi.org/10.1093/nar/29.2.515
Lengler, Johannes ; Krausz, Eberhard ; Tomarev, Stanislav ; Prescott, Alan ; Quinlan, Roy A. ; Graw, Jochen. / Antagonistic action of Six3 and Prox1 at the γ-crystallin promoter. In: Nucleic Acids Research. 2001 ; Vol. 29, No. 2. pp. 515-526.
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Lengler, J, Krausz, E, Tomarev, S, Prescott, A, Quinlan, RA & Graw, J 2001, 'Antagonistic action of Six3 and Prox1 at the γ-crystallin promoter', Nucleic Acids Research, vol. 29, no. 2, pp. 515-526. https://doi.org/10.1093/nar/29.2.515

Antagonistic action of Six3 and Prox1 at the γ-crystallin promoter. / Lengler, Johannes; Krausz, Eberhard; Tomarev, Stanislav; Prescott, Alan; Quinlan, Roy A.; Graw, Jochen (Lead / Corresponding author).

In: Nucleic Acids Research, Vol. 29, No. 2, 15.01.2001, p. 515-526.

Research output: Contribution to journalArticle

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