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Barrier to autointegration factor interacts with the cone-rod homeobox and represses its transactivation function.

http://www.ncbi.nlm.nih.gov/pubmed/12215455

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.

Pubmed ID: 12215455 RIS Download

Mesh terms: Amino Acid Sequence | Animals | Base Sequence | Cattle | Cell Line | Cloning, Molecular | Computational Biology | DNA Primers | DNA-Binding Proteins | Gene Library | Homeodomain Proteins | Humans | Mice | Molecular Sequence Data | Nuclear Proteins | Polymerase Chain Reaction | Rats | Retina | Saccharomyces cerevisiae | Sequence Alignment | Sequence Homology, Amino Acid | Species Specificity | Trans-Activators | Transcriptional Activation | Transfection

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