Specific Pax-6/microphthalmia transcription factor interactions involve their DNA-binding domains and inhibit transcriptional properties of both proteins
N. Planque et al., Specific Pax-6/microphthalmia transcription factor interactions involve their DNA-binding domains and inhibit transcriptional properties of both proteins, J BIOL CHEM, 276(31), 2001, pp. 29330-29337
Pax-6 and microphthalmia transcription factor (Mitf) are required for prope
r eye development. Pax-6, expressed in both the neuroretina and pigmented r
etina, has two DNA-binding domains: the paired domain and the homeodomain.
Mice homozygous for Pax-6 mutations are anophthalmic. Mitf, a basic helix-l
oop-helix leucine zipper (b-HLH-LZ) transcription factor associated with th
e onset and maintenance of pigmentation, identifies the retinal pigmented e
pithelium during eye development. Loss of Mitf function results in the form
ation of an ectopic neuroretina at the expense of the dorsal retinal pigmen
ted epithelium. In the present study, we investigated the interaction betwe
en Pax-6 and Mitf. In transient transfection-expression experiments, we fou
nd that transactivating effects of Pax-6 and Mitf on their respective targe
t promoters were strongly inhibited by co-transfection of both transcriptio
n factors. This repression was due to direct protein/protein interactions i
nvolving 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 p
igmented epithelium development.