Differential DNA binding activities of the transcription factors AP-1 and Oct-1 during light-induced apoptosis of photoreceptors.
The activity of transcription factors like AP-1 and Oct-1 is critical for the regulation of gene expression. Whereas Oct-1 mainly regulates the expression of housekeeping genes, AP-1 is often involved in cellular responses to external stimuli and plays an essential role in the regulation of light-induced apoptosis of mouse retinal photoreceptors. In this study, we investigated AP-1 and Oct-1 DNA binding activity and AP-1 complex composition in the mouse retina during light-induced photoreceptor apoptosis. AP-1 DNA binding activity was low in dark-adapted animals but was transiently elevated within 12 h after exposure of mice to apoptosis-inducing levels of white fluorescent light. Maximal AP-1 activity was found 6 h after light-exposure. Antibody interference analysis at 6 h after damaging light exposure and under normal light conditions revealed that the major fraction of AP-1 consists of c-Fos/JunD heterodimers in both situations. In contrast to AP-1, Oct-1 DNA binding activity was maximal in dark-adapted animals and was reduced during photoreceptor apoptosis. Transient induction of AP-1 (c-Fos/JunD) and inactivation of Oct-1 may be crucial events for light-mediated apoptosis of retinal photoreceptors.
Department of Ophthalmology, University Hospital, Zurich, Switzerland. hafezi@opht.unizh.ch
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Hafezi
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Marti
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Grimm
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Wenzel
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D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003623:Dark Adaptation; D005786:Gene Expression Regulation; D051863:Host Cell Factor C1; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050811:Octamer Transcription Factor-1; D010786:Photoreceptor Cells / Q000166:cytology / Q000528:radiation effects*; D012160:Retina / Q000378:metabolism; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; C494166:Pou2f1 protein, mouse; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D004247:DNA