An everted repeat mediates retinoic acid induction of the gamma F-crystallin gene: evidence of a direct role for retinoids in lens development
| Autor: | Mark Tini, Vincent Giguère, L C Tsui, G Otulakowski, M L Breitman |
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| Rok vydání: | 1993 |
| Předmět: |
Cell signaling
Cellular differentiation Molecular Sequence Data Response element Retinoic acid Tretinoin Chick Embryo Biology Retinoid X receptor Mice chemistry.chemical_compound Crystallin Lens Crystalline Genetics medicine Animals Amino Acid Sequence Repetitive Sequences Nucleic Acid Base Sequence Crystallins Cell biology chemistry Nuclear receptor Developmental Biology medicine.drug |
| Zdroj: | Genes & Development. 7:295-307 |
| ISSN: | 1549-5477 0890-9369 |
| DOI: | 10.1101/gad.7.2.295 |
| Popis: | The vertebrate lens is a classical system for examining mechanisms of tissue determination and differentiation, yet little is known about the signaling molecules controlling its development. Here, we report that retinoic acid (RA), a substance known for its teratogenic effects on the eye and as a natural endogenous morphogenetic agent, acts as a regulator of gene expression in the lens. We have identified a novel type of RA response element (RARE) within the lens-specific mouse gamma F-crystallin promoter, consisting of two (A/G)GGTCA motifs in an everted arrangement spaced by 8 nucleotides. This element (gamma F-RARE) mediates activation of the gamma F-crystallin promoter by ligand-activated endogenous lens cell RA receptors (RARs) and confers RA responsiveness when linked to a heterologous promoter. gamma F-RARE is bound in vitro by RAR/RXR heterodimers, and both receptors cooperate in vivo to trans-activate this element. These observations demonstrate a direct effect of RA on lens-specific gene expression and reveal a novel role for retinoids in the development and homeostasis of the mammalian eye. |
| Databáze: | OpenAIRE |
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