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

Xuejiao Wang, Siqun Xu, Carlo Rivolta, Lili Y. Li, Guang Hua Peng, Prabodh K. Swain, Ching Hwa Sung, Anand Swaroop, Eliot L. Berson, Thaddeus P. Dryja, Shiming Chen

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

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 tissueor cell type-specific gene expression by interacting with homeodomain transcription factors.

Original languageEnglish
Pages (from-to)43288-43300
Number of pages13
JournalJournal of Biological Chemistry
Volume277
Issue number45
DOIs
StatePublished - Nov 8 2002

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