Involvement of SOX proteins in lens-specific activation of crystallin genes.
We have studied the mechanism of delta 1-crystallin gene activation, which occurs early in lens cell differentiation, and have previously shown that an essential element of the delta 1-crystallin enhancer is bound by a group of nuclear factors, delta EF2, among which delta EF2a is 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 structurally related to the sex-determining factor SRY. Sox-2 is expressed at high levels in the early developing lens in both chicken and mouse embryos. Overexpression of delta EF2a/cSOX-2 increased delta 1-crystallin enhancer activity to a plateau in lens cells, but not in fibroblasts, consistent with the previously drawn conclusion that delta EF2a activates transcription only in concert with another factor present in the lens. This result supports the model that SOX proteins act as architectural components in the activating complex formed on an enhancer, as indicated for another HMG domain protein, lymphoid enhancer binding factor 1 (LEF-1). We also show that SOX protein binding is essential for lens-specific promoter activity of the mouse gamma F-crystallin gene. This work is the first to show delta- and gamma-crystallin genes as examples of direct regulatory targets of SOX proteins and provides evidence that diversified crystallin genes are regulated, at least partly, by a common mechanism.
Kamachi
Y
Y
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Sockanathan
S
S
Liu
Q
Q
Breitman
M
M
Lovell-Badge
R
R
Kondoh
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002645:Chickens; D003001:Cloning, Molecular; D003459:Crystallins / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D024002:HMGB Proteins; D006801:Humans; D007908:Lens, Crystalline / Q000196:embryology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D010455:Peptides; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D055748:SOXB1 Transcription Factors; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D015533:Transcriptional Activation
D003459:Crystallins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D009687:Nuclear Proteins; D010455:Peptides; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors