Distinct roles of SOX2, Pax6 and Maf transcription factors in the regulation of lens-specific delta1-crystallin enhancer.
BACKGROUND
The eye lens provides a good model for the study of regulation of cell differentiation, in which lens-specific delta1-crystallin expression serves as an indicator of the differentiated state of the cells. It has been indicated that the SOX2, Pax6 and Maf proteins are the major regulators of lens cell differentiation. To clarify the individual roles of these transcription factors, we analysed their participation in regulation of the delta1-crystallin enhancer.


RESULTS
We defined the major binding sites of SOX2, Pax6 and Maf transcription factors in the delta1-crystallin enhancer and assessed the effect of mutations at these sites in the cultured lens epithelial cells and in developing lenses of transgenic mouse embryos. SOX2 (or SOX1/SOX3) is essential for activation of the enhancer under all conditions. Pax6 bound at the deltaEF3 site is required for activation of the enhancer, while Pax6 at the Pax6U site appears to be involved in the Pax6-dependent suppression of the enhancer. In contrast, Maf proteins are only required for high enhancer activity in lens fibre cells.


CONCLUSIONS
The distinct roles of these transcription factors in the regulation of delta1-crystallin enhancer would tend to indicate their individual functions in lens differentiation. The activity of SOX2 and the related SOX1/3 is essential at all stages of lens development as transcriptional activators. Pax6, although it is required in all steps, probably exerts complex regulatory effects, since it possesses both the potential to activate and repress. The major function of Maf proteins presumably resides in the activation of the genes in lens fibre cells.
Muta
Mayumi
M
Laboratory of Developmental Biology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.
Kamachi
Yusuke
Y
Yoshimoto
Aki
A
Higashi
Yujiro
Y
Kondoh
Hisato
H
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D003459:Crystallins / Q000235:genetics*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic; D005136:Eye Proteins; D024002:HMGB Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007908:Lens, Crystalline / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D003459:Crystallins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D024002:HMGB Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors