Functional domains of the cone-rod homeobox (CRX) transcription factor

The paired-like homeodomain transcription factor CRX (cone-rod homeobox) is involved in regulating photoreceptor gene expression and rod outer segment development. Mutations in CRX have been associated with several retinal de generative diseases. These conditions range from Leber congenital amaurosis (a severe cone and rod degeneration of childhood onset) to adult onset con e-rod dystrophy and retinitis pigmentosa tan adult onset condition that pri marily affects rods). The goal of this study is to better understand the mo lecular basis of CRX function and to provide insight into how mutations in CRX cause such a variety of clinical phenotypes. We performed deletion anal ysis in conjunction with DNA binding and transient transfection-based trans activation studies to identify the functional domains within CRX. DNA bindi ng requires a complete homeodomain. Furthermore, truncated proteins that di d not contain an intact homeodomain failed to demonstrate detectable expres sion in tissue culture upon transfection. Transactivation analysis indicate d that both the OTX tail and the WSP domain are important for controlling p ositive regulatory activity of CRX interestingly, the mapped CRX transactiv ation domains were also critical when coexpressed with NRL, Specifically, t he synergy between CRX and NRL was constant regardless of which CRX variant was used.