SOX7 and SOX17 regulate the parietal endoderm-specific enhancer activity of mouse laminin alpha1 gene.
Laminin-1 is the major component of embryonic basement membrane and consists of alpha1, beta1, and gamma1 chains. The expression of laminin-1 is induced in mouse F9 embryonal carcinoma cells upon differentiation into parietal endoderm cells. We recently identified a parietal endoderm-specific enhancer in the mouse laminin alpha1 (Lama1) gene and showed that Sp1/Sp3 and YY1 transcription factors were involved in the enhancer activity. Although here we identified that NF-Y binds to the enhancer sequence between Sp1/Sp3- and YY1-binding sites, all these transcription factors are ubiquitously expressed and thus are not sufficient to explain parietal endoderm-specific enhancer activity. In the present study, we further showed that SOX7 and SOX17 are involved in the regulation of parietal endoderm-specific enhancer activity of the mouse Lama1 gene. Northern blot analysis revealed that the steady-state levels of mouse Sox7 and Sox17 mRNAs increased in parallel with that of Lama1 mRNA during the differentiation of F9 cells. Both SOX7 and SOX17 markedly trans-activated the transcription of the Lama1 enhancer-reporter construct in undifferentiated F9 cells in a manner dependent on high mobility group box-mediated DNA binding. Electrophoretic mobility shift assays and mutational analyses revealed that SOX7 and SOX17 bound specifically to two SOX-binding sites within the Lama1 enhancer, and that these SOX-binding sites functioned synergistically to confer the trans-activation by SOX7 and SOX17. Furthermore, this trans-activation was dependent on the integrity of the binding sites for Sp1/Sp3 and NF-Y located at upstream of the two SOX-binding sites. These results indicate that the transcription of the mouse Lama1 gene during the differentiation of F9 cells is controlled by a combination of the actions of the ubiquitous factors, Sp1/Sp3 and NF-Y, and the parietal endoderm-specific factors, SOX7 and SOX17.
Niimi
Tomoaki
T
Sekiguchi Biomatrix Signaling Project, ERATO, Japan Science and Technology Agency, Aichi Medical University, Karimata, Yazako, Nagakute, Aichi 480-1195, Japan.
Hayashi
Yoshitaka
Y
Futaki
Sugiko
S
Sekiguchi
Kiyotoshi
K
D000818:Animals; D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D004707:Endoderm / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000502:physiology*; D006609:High Mobility Group Proteins / Q000502:physiology*; D007797:Laminin / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D055760:SOXF Transcription Factors; D014157:Transcription Factors / Q000502:physiology*
D023081:CCAAT-Binding Factor; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D007797:Laminin; D012333:RNA, Messenger; C109188:SOX17 protein, human; D055760:SOXF Transcription Factors; C102515:Sox7 protein, mouse; D014157:Transcription Factors