Identification and characterization of a critical CP2-binding element in the human interleukin-4 promoter Journal Article
| Authors: | Casolaro, V.; Keane-Myers, A. M.; Swendeman, S. L.; Steindler, C.; Zhong, F. M.; Sheffery, M.; Georas, S. N.; Ono, S. J. |
| Article Title: | Identification and characterization of a critical CP2-binding element in the human interleukin-4 promoter |
| Abstract: | Expression of cytokine genes in T cells is thought to result from a complex network of antigen- and mitogen-activated transcriptional regulators. CP2, a factor homologous to Drosophila Elf-1 and previously found to be a critical regulator of several viral and cellular genes in response to developmental signals, is rapidly activated in T helper (Th) cells in response to mitogenic stimulation. Here we show that overexpression of CP2 enhances interleukin (IL)-4 promoter-driven chloramphenicol acetyltransferase expression, while repressing IL-2 promoter activity, in transiently transfected Jurkat cells. A CP2-protected element, partially overlapping the nuclear factor of activated T cell-binding P2 sequence, was required for IL-4 promoter activation in CPS-overexpressing Jurkat cells. This CPS-response element is the site of a cooperative interaction between CP2 and an inducible heteromeric co-factor(s). Mutation of conserved nucleotide contacts within the CPa-response element prevented CP2 binding and significantly reduced constitutive and induced IL-4 promoter activity. Expression of a CP2 mutant lacking the Elf-l-homology region of the DNA-binding domain inhibited IL-4 promoter activity in a dominant negative fashion in transiently transfected Jurkat cells. Moreover, overexpressed CP2 markedly enhanced, while its dominant negative mutant consistently suppressed, expression of the endogenous IL-4 gene in the murine Th2 cell line DIG. Taken together, these findings point to CP2 as a critical IL-4 transactivator in Th cells. |
| Keywords: | in-vitro; long terminal repeat; dna-binding; nuclear factor; activated t-cells; simplex virus type-1; transcription factor cp2; helper cell subsets; stage selector protein; il-4 gene-expression |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 275 |
| Issue: | 47 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2000-11-24 |
| Start Page: | 36605 |
| End Page: | 36611 |
| Language: | English |
| ACCESSION: | WOS:000165577700022 |
| DOI: | 10.1074/jbc.M007086200 |
| PROVIDER: | wos |
| PUBMED: | 10973979 |
| Notes: | Article -- Source: Wos |
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