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J. Biol. Chem., Vol. 276, Issue 31, 29330-29337, August 3, 2001
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From the CNRS UMR 146, Institut Curie Section Recherche, Centre
Universitaire Bâtiment 110, 91405 Orsay Cedex, France
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.
Specific Pax-6/Microphthalmia Transcription Factor
Interactions Involve Their DNA-binding Domains and Inhibit
Transcriptional Properties of Both Proteins*
*
This work was supported by grants from the Centre National
de la Recherche Scientifique, the Institut Curie, the Association Retina France, the Association pour la Recherche contre le Cancer, the
Ligue Nationale contre le Cancer, the Fondation pour la Recherche Médicale, and the Association de Secours des Amis des Sciences.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.:
33-1 69 86 71 53; Fax: 33-1 69 07 45 25; E-mail:
Simon.Saule@curie.u-psud.fr.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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