Specific Pax-6/microphthalmia transcription factor interactions involve their DNA-binding domains and inhibit transcriptional properties of both proteins.
Pax-6 and microphthalmia transcription factor (Mitf) are required for proper eye development. Pax-6, expressed in both the neuroretina and pigmented retina, has two DNA-binding domains: the paired domain and the homeodomain. Mice homozygous for Pax-6 mutations are anophthalmic. Mitf, a basic helix-loop-helix leucine zipper (b-HLH-LZ) transcription factor associated with the onset and maintenance of pigmentation, identifies the retinal pigmented epithelium during eye development. Loss of Mitf function results in the formation of an ectopic neuroretina at the expense of the dorsal retinal pigmented epithelium. In the present study, we investigated the interaction between Pax-6 and Mitf. In transient transfection-expression experiments, we found that transactivating effects of Pax-6 and Mitf on their respective target promoters were strongly inhibited by co-transfection of both transcription factors. This repression was due to direct protein/protein interactions involving both Pax-6 DNA-binding domains and the Mitf b-HLH-LZ domain. These results suggest that Pax-6/Mitf interactions may be critical for retinal pigmented epithelium development.
Planque
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CNRS UMR 146, Institut Curie Section Recherche, Centre Universitaire Bâtiment 110, 91405 Orsay Cedex, France.
Leconte
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Coquelle
F M
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Martin
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Saule
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D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D006224:Cricetinae; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D018257:Helix-Loop-Helix Motifs; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006720:Homozygote; D016350:Leucine Zippers; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D014176:Protein Biosynthesis; D011784:Quail; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins; D015183:Restriction Mapping; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D015342:DNA Probes; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins