CRX (cone-rod homeobox) is shown to play an important role on the photoreceptor cell maturation and maintenance. However, little is known about the molecular mechanism how CRX potentiates transcription. Here, we investigated the effect of several coactivators (p300/CEP, SRC-1, TIF2, and ATB1) on the transactivation function of CRX. The transient expression assay with a luciferase reporter gene showed that only p300/CBP potentiates the transactivation function of CRX Furthermore, by interaction studies in. rico (a mammalian two-hybrid assay) and in vitro (a pulldown assay), p300/CBP was found to directly bind CRY through their C-terminal domains. The C-terminal domain of CRX was mapped as a transactivation domain to associate with p300/CBP. Taken together, our results demonstrate that p300/CBP acts as one of the coactivators of CRX