Article: article from journal or magazin.
Barrier to autointegration factor interacts with the cone-rod homeobox and represses its transactivation function.
Journal of Biological Chemistry
Crx (cone-rod homeobox) is a homeodomain transcription factor implicated in regulating the expression of photoreceptor and pineal genes. To identify proteins that interact with Crx in the retina, we carried out a yeast two-hybrid screen of a retinal cDNA library. One of the identified clones encodes Baf (barrier to autointegration factor), which was previously shown to have a role in mitosis and retroviral integration. Additional biochemical assays provided supporting evidence for a Baf-Crx interaction. The Baf protein is detectable in all nuclear layers of the mouse retina, including the photoreceptors and the bipolar cells where Crx is expressed. Transient transfection assays with a rhodopsin-luciferase reporter in HEK293 cells demonstrate that overexpression of Baf represses Crx-mediated transactivation, suggesting that Baf acts as a negative regulator of Crx. Consistent with this role for Baf, an E80A mutation of CRX associated with cone-rod dystrophy has a higher than normal transactivation potency but a reduced interaction with Baf. Although our studies did not identify a causative Baf mutation in retinopathies, we suggest that Baf may contribute to the phenotype of a photoreceptor degenerative disease by modifying the activity of Crx. In view of the ubiquitous expression of Baf, we hypothesize that it may play a role in regulating tissue- or cell type-specific gene expression by interacting with homeodomain transcription factors.
Amino Acid Sequence, Animals, Base Sequence, Cattle, Cell Line, Cloning, Molecular, Computational Biology, DNA Primers, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Gene Library, Homeodomain Proteins/metabolism, Humans, Mice, Molecular Sequence Data, Nuclear Proteins, Polymerase Chain Reaction, Rats, Retina/metabolism, Saccharomyces cerevisiae/genetics, Sequence Alignment, Sequence Homology, Amino Acid, Species Specificity, Trans-Activators/metabolism, Transcriptional Activation, Transfection
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