Crystallins are a diverse group of abundant soluble proteins that are responsible for the refractive properties of the transparent eye lens. We showed previously that Pax-6 can activate the ␣B-crystallin/small heat shock protein promoter via the lens-specific regulatory regions LSR1 (؊147/؊118) and LSR2 (؊78/؊46). Here we demonstrate that retinoic acid can induce the accumulation of ␣B-crystallin in N/N1003A lens cells and that retinoic acid receptor heterodimers (retinoic acid

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... X receptor; RAR/RXR) can transactivate LSR1 and LSR2 in cotransfection experiments. DNase I footprinting experiments demonstrated that purified RAR/RXR heterodimers will occupy sequences resembling retinoic acid response elements within LSR1 and LSR2. Electrophoretic mobility shift assays using antibodies indicated that LSR1 and LSR2 can interact with endogenous RAR/RXR complexes in extracts of cultured lens cells. Pax-6 and RAR/RXR together had an additive effect on the activation of ␣B-promoter in the transfected lens cells. Thus, the ␣B-crystallin gene is activated by Pax-6 and retinoic acid receptors, making these transcription factors examples of proteins that have critical roles in early development as well as in the expression of proteins characterizing terminal differentiation.