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

Overview

abstract

  • 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.

publication date

  • September 4, 2002

Research

keywords

  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Transcriptional Activation

Identity

Scopus Document Identifier

  • 18644386771

Digital Object Identifier (DOI)

  • 10.1074/jbc.M207952200

PubMed ID

  • 12215455

Additional Document Info

volume

  • 277

issue

  • 45