TY - JOUR
T1 - Direct interaction of C/EBPδ and Sp1 at the GC-enriched promoter region synergizes the IL-10 gene transcription in mouse macrophage
AU - Chiang, Ben Tzu
AU - Liu, Yi Wen
AU - Chen, Ben Kuen
AU - Wang, Ju Ming
AU - Chang, Wen Chang
PY - 2006/9
Y1 - 2006/9
N2 - We previously reported that LPS activates the transcription of the IL-10 gene through the Sp1 and C/EBP binding sites and indicated that Sp1, C/EBPβ and C/EBPδ can coactivate the IL-10 gene expression in mouse macrophage cells [Liu Y.-W., Tseng H.-P., Chen L.-C., Chen B.-K., Chang W.-C. J. Immunol. 171: 821-828, 2003]. In the present report, we demonstrated the direct physical interaction between C/EBPδ and Sp1, and also mapped the interaction domains of these two proteins. C/EBPδ binds to Sp1 via its basic region leucine zipper domain. The C-terminus of Sp1 was also the major region interacting with C/EBPδ. However, both glutamine- and serine/threonine- rich homologus regions of Sp1 also interacted with C/EBPδ. The binding of Sp1 and C/EBPδ as a complex to the Sp1 binding site on the promoter of IL-10 was further confirmed by using the DNA affinity precipitation assay. By using Sp1-deficient SL2 cells, we also found that the overexpressions of C/EBPδ and Sp1 synergically activate the transcriptional activity of IL-10 gene. Taken together, our present results revealed a novel mechanism of a superactivation of Sp1 by C/EBPδ via a direct interaction between these two transcription factors leading to the activation of the IL-10 gene in mouse macrophage cells.
AB - We previously reported that LPS activates the transcription of the IL-10 gene through the Sp1 and C/EBP binding sites and indicated that Sp1, C/EBPβ and C/EBPδ can coactivate the IL-10 gene expression in mouse macrophage cells [Liu Y.-W., Tseng H.-P., Chen L.-C., Chen B.-K., Chang W.-C. J. Immunol. 171: 821-828, 2003]. In the present report, we demonstrated the direct physical interaction between C/EBPδ and Sp1, and also mapped the interaction domains of these two proteins. C/EBPδ binds to Sp1 via its basic region leucine zipper domain. The C-terminus of Sp1 was also the major region interacting with C/EBPδ. However, both glutamine- and serine/threonine- rich homologus regions of Sp1 also interacted with C/EBPδ. The binding of Sp1 and C/EBPδ as a complex to the Sp1 binding site on the promoter of IL-10 was further confirmed by using the DNA affinity precipitation assay. By using Sp1-deficient SL2 cells, we also found that the overexpressions of C/EBPδ and Sp1 synergically activate the transcriptional activity of IL-10 gene. Taken together, our present results revealed a novel mechanism of a superactivation of Sp1 by C/EBPδ via a direct interaction between these two transcription factors leading to the activation of the IL-10 gene in mouse macrophage cells.
KW - Cytokines
KW - Gene regulation
KW - Monocytes/macrophages
KW - Signal transduction
KW - Transcription factors
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U2 - 10.1007/s11373-006-9101-y
DO - 10.1007/s11373-006-9101-y
M3 - Article
C2 - 16871431
AN - SCOPUS:33749343200
VL - 13
SP - 621
EP - 635
JO - Journal of Biomedical Science
JF - Journal of Biomedical Science
SN - 1021-7770
IS - 5
ER -