INVOLVEMENT OF SOX PROTEINS IN LENS-SPECIFIC ACTIVATION OF CRYSTALLINGENES

We have studied the mechanism of delta 1-crystallin gene activation, w hich occurs early in lens cell differentiation, and have previously sh own that an essential element of the delta 1-crystallin enhancer is bo und by a group of nuclear factors, delta EF2, among which delta EF2a i s highly enriched in lens cells. In this report we show that the cDNA of delta EF2a codes for the chicken SOX-2 protein (cSOX-2), which is s tructurally related to the sex-determining factor SRY. Sox-2 is expres sed at high levels in the early developing lens in both chicken and mo use embryos. Overexpression of delta EF2a/cSOX-2 increased delta 1-cry stallin enhancer activity to a plateau in lens cells, but not in fibro blasts, consistent with the previously drawn conclusion that delta EF2 a activates transcription only in concert with another factor present in the lens. This result supports the model that SOX proteins act as a rchitectural components in the activating complex formed on an enhance r, as indicated for another HMG domain protein, lymphoid enhancer bind ing factor 1 (LEF-1). We also show that SOX protein binding is essenti al for lens-specific promoter activity of the mouse gamma F-crystallin gene, This work is the first to show delta- and gamma-crystallin gene s as examples of direct regulatory targets of SOX proteins and provide s evidence that diversified crystallin genes are regulated, at least p artly, by a common mechanism.