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

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

Authors

  • Wang X
  • Xu S
  • Rivolta C
  • Li LY
  • Peng GH
  • Swain PK
  • Sung CH
  • Swaroop A
  • Berson EL
  • Dryja TP
  • Chen S

Journal

The Journal of biological chemistry

Publication Data

November 8, 2002

Associated Grants

  • Agency: NEI NIH HHS, Id: EY00169
  • Agency: NEI NIH HHS, Id: EY02687
  • Agency: NEI NIH HHS, Id: EY08683
  • Agency: NEI NIH HHS, Id: EY11115
  • Agency: NEI NIH HHS, Id: EY12543
  • Agency: NEI NIH HHS, Id: R01 EY011307
  • Agency: NEI NIH HHS, Id: R01 EY012543

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