Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
The weak, fine-tuned binding of ubiquitous transcription factors to the Il-2 enhancer contributes to its T cell-restricted activity.
Hentsch B
,
Mouzaki A
,
Pfeuffer I
,
Rungger D
,
Serfling E
.
???displayArticle.abstract???
The T lymphocyte-specific enhancers of the murine and human Interleukin 2 (Il-2) genes harbour several binding sites for ubiquitous transcription factors. All these sites for the binding of AP-1, NF-kB or Oct-1 are non-canonical sites, i.e. they differ in one or a few base pairs from consensus sequences for the optimal binding of these factors. Although the factors bind weakly to these sites, the latter are functionally important because their mutation to non-binding sites results in a decrease of inducible activity of the Il-2 enhancer. Conversion of three sites to canonical binding sites of Octamer factors, AP-1 and NF-kB results in a drastic increase in enhancer activity and the induction of the Il-2 enhancer in non-T cells, such as B cell lines, murine L cells and human HeLa cells. The introduction of two or three canonical sites into the enhancer leads to a further increase of its activity. Il-2 enhancer induction is also observed in B cells when the concentration of AP-1 and Oct factors increases as a result of cotransfections with FosB and Octamer expression plasmids. When Il-2 enhancer constructs carrying canonical factor binding sites were injected into Xenopus oocytes the strong binding of ubiquitous factors substantially overcomes the silencing effect of negatively acting factors present in resting primary T lymphocytes. These results suggest a fine-tuned interplay between ubiquitous and lymphoid-specific factors binding to and transactivating the Il-2 enhancer and show that the binding affinity of ubiquitous factors to the enhancer contributes to its cell-type specific activity. Moreover, we believe that a dramatic increase of transcriptional activity brought about by single point mutations at strategic important factor binding sites may also have relevance to the activation of nuclear oncogenes.
Angel,
Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor.
1987, Pubmed
Angel,
Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor.
1987,
Pubmed
Angel,
The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1.
1988,
Pubmed
Brabletz,
The immunosuppressives FK 506 and cyclosporin A inhibit the generation of protein factors binding to the two purine boxes of the interleukin 2 enhancer.
1991,
Pubmed
Briegel,
One base pair change abolishes the T cell-restricted activity of a kB-like proto-enhancer element from the interleukin 2 promoter.
1991,
Pubmed
Brunvand,
Nuclear factors interacting with the mitogen-responsive regulatory region of the interleukin-2 gene.
1988,
Pubmed
Crabtree,
Contingent genetic regulatory events in T lymphocyte activation.
1989,
Pubmed
Durand,
A 275 basepair fragment at the 5' end of the interleukin 2 gene enhances expression from a heterologous promoter in response to signals from the T cell antigen receptor.
1987,
Pubmed
Durand,
Characterization of antigen receptor response elements within the interleukin-2 enhancer.
1988,
Pubmed
Faisst,
Compilation of vertebrate-encoded transcription factors.
1992,
Pubmed
Fujita,
Regulation of human interleukin-2 gene: functional DNA sequences in the 5' flanking region for the gene expression in activated T lymphocytes.
1986,
Pubmed
Gerster,
Cell type-specificity elements of the immunoglobulin heavy chain gene enhancer.
1987,
Pubmed
Hoyos,
Kappa B-specific DNA binding proteins: role in the regulation of human interleukin-2 gene expression.
1989,
Pubmed
Jain,
The AP-1 site at -150 bp, but not the NF-kappa B site, is likely to represent the major target of protein kinase C in the interleukin 2 promoter.
1992,
Pubmed
Kamps,
The promoter of the human interleukin-2 gene contains two octamer-binding sites and is partially activated by the expression of Oct-2.
1990,
Pubmed
Kemler,
Promoters with the octamer DNA motif (ATGCAAAT) can be ubiquitous or cell type-specific depending on binding affinity of the octamer site and Oct-factor concentration.
1991,
Pubmed
Lenardo,
NF-kappa B protein purification from bovine spleen: nucleotide stimulation and binding site specificity.
1988,
Pubmed
Lewin,
Oncogenic conversion by regulatory changes in transcription factors.
1991,
Pubmed
Luckow,
CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements.
1987,
Pubmed
Luthman,
High efficiency polyoma DNA transfection of chloroquine treated cells.
1983,
Pubmed
Matthias,
Eukaryotic expression vectors for the analysis of mutant proteins.
1989,
Pubmed
Mitchell,
Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins.
1989,
Pubmed
Mouzaki,
Silencing and trans-activation of the mouse IL-2 gene in Xenopus oocytes by proteins from resting and mitogen-induced primary T-lymphocytes.
1991,
Pubmed
,
Xenbase
Müller,
A cloned octamer transcription factor stimulates transcription from lymphoid-specific promoters in non-B cells.
1988,
Pubmed
Mumberg,
Alternative splicing of fosB transcripts results in differentially expressed mRNAs encoding functionally antagonistic proteins.
1991,
Pubmed
Novak,
Regulatory anatomy of the murine interleukin-2 gene.
1990,
Pubmed
Pierce,
Oligonucleotide that binds nuclear factor NF-kappa B acts as a lymphoid-specific and inducible enhancer element.
1988,
Pubmed
Randak,
Cyclosporin A suppresses the expression of the interleukin 2 gene by inhibiting the binding of lymphocyte-specific factors to the IL-2 enhancer.
1990,
Pubmed
Ryder,
A gene activated by growth factors is related to the oncogene v-jun.
1988,
Pubmed
Schöler,
Octamania: the POU factors in murine development.
1991,
Pubmed
Schöler,
Octamer binding proteins confer transcriptional activity in early mouse embryogenesis.
1989,
Pubmed
Schreiber,
Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells.
1989,
Pubmed
Schreiber,
Identification of a novel lymphoid specific octamer binding protein (OTF-2B) by proteolytic clipping bandshift assay (PCBA).
1988,
Pubmed
Schuermann,
An expression vector system for stable expression of oncogenes.
1990,
Pubmed
Serfling,
Ubiquitous and lymphocyte-specific factors are involved in the induction of the mouse interleukin 2 gene in T lymphocytes.
1989,
Pubmed
Shaw,
Identification of a putative regulator of early T cell activation genes.
1988,
Pubmed
Shibuya,
Involvement of a common transcription factor in the regulated expression of IL-2 and IL-2 receptor genes.
1989,
Pubmed
Stern,
The herpes simplex virus trans-activator VP16 recognizes the Oct-1 homeo domain: evidence for a homeo domain recognition subdomain.
1991,
Pubmed
Sturm,
The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain.
1988,
Pubmed
Tanaka,
Differential transcriptional activation by Oct-1 and Oct-2: interdependent activation domains induce Oct-2 phosphorylation.
1990,
Pubmed
Tanaka,
Promoter-selective activation domains in Oct-1 and Oct-2 direct differential activation of an snRNA and mRNA promoter.
1992,
Pubmed
Ullman,
Activation of early gene expression in T lymphocytes by Oct-1 and an inducible protein, OAP40.
1991,
Pubmed
Williams,
Identification of a zinc finger protein that inhibits IL-2 gene expression.
1991,
Pubmed
Williams,
Two regions within the human IL-2 gene promoter are important for inducible IL-2 expression.
1988,
Pubmed
Zabel,
DNA binding of purified transcription factor NF-kappa B. Affinity, specificity, Zn2+ dependence, and differential half-site recognition.
1991,
Pubmed
