scholarly journals HLA class I heavy-chain gene promoter elements mediating synergy between tumor necrosis factor and interferons.

1994 ◽  
Vol 14 (2) ◽  
pp. 1322-1332 ◽  
Author(s):  
D R Johnson ◽  
J S Pober
Keyword(s):  
Heavy Chain ◽  
Tumor Necrosis ◽  
Hla Class I ◽  
Class I ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Ifn Gamma ◽  
Histocompatibility Complex ◽  
Nuclear Factors ◽  
Necrosis Factor

The cytokines tumor necrosis factor (TNF), beta interferon (IFN-beta), and IFN-gamma increase major histocompatibility complex class I molecule expression. A greater than additive (i.e., synergistic) induction of class I heavy-chain mRNA is observed in HeLa cells treated with TNF in combination with either type of IFN. To define the cis-acting elements mediating cytokine synergy, the promoter of a human major histocompatibility complex class I heavy-chain gene (HLA-B7) was placed in front of a reporter gene and transfected into HeLa cells. Deletion analysis mapped the elements required for synergy to a 40-bp region containing a kappa B-like element, which is necessary for the response to TNF, and an interferon consensus sequence (ICS), which is necessary for the responses to IFNs. When the orientation of these elements was reversed or their normal 20-bp spacing was reduced by 5 or 10 bp, i.e., one half or one full turn of the DNA helix, essentially equivalent responses were obtained, suggesting that these parameters are not critical. In electromobility shift assays, a p50-containing NF-kappa B nuclear factor from TNF-treated cells binds kappa B-containing probes, and ISGF-2 from IFN-gamma-treated cells binds ICS-containing probes. A probe containing both the kappa B and ICS elements (kappa B-ICS) forms a novel complex with nuclear factors isolated from cells treated with both TNF and IFN-gamma; this complex also forms when nuclear factors from individually cytokine-treated cells are mixed in vitro. The natural variant ICS found in HLA-A responds to IFN-gamma and can mediate synergy with TNF. However, the variant kappa B found in HLA-C does not respond to TNF, nor can it mediate synergy between TNF and IFN-gamma. These observations suggest that synergy between TNF and IFNs in the induction of HLA class I gene expression results from the sum of individual interactions of cytokine-activated enhancer-binding factors with the transcription initiation complex.

scholarly journals HLA class I heavy-chain gene promoter elements mediating synergy between tumor necrosis factor and interferons

1994 ◽  
Vol 14 (2) ◽  
pp. 1322-1332
Author(s):  
D R Johnson ◽  
J S Pober
Keyword(s):  
Heavy Chain ◽  
Tumor Necrosis ◽  
Hla Class I ◽  
Class I ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Ifn Gamma ◽  
Histocompatibility Complex ◽  
Nuclear Factors ◽  
Necrosis Factor

The cytokines tumor necrosis factor (TNF), beta interferon (IFN-beta), and IFN-gamma increase major histocompatibility complex class I molecule expression. A greater than additive (i.e., synergistic) induction of class I heavy-chain mRNA is observed in HeLa cells treated with TNF in combination with either type of IFN. To define the cis-acting elements mediating cytokine synergy, the promoter of a human major histocompatibility complex class I heavy-chain gene (HLA-B7) was placed in front of a reporter gene and transfected into HeLa cells. Deletion analysis mapped the elements required for synergy to a 40-bp region containing a kappa B-like element, which is necessary for the response to TNF, and an interferon consensus sequence (ICS), which is necessary for the responses to IFNs. When the orientation of these elements was reversed or their normal 20-bp spacing was reduced by 5 or 10 bp, i.e., one half or one full turn of the DNA helix, essentially equivalent responses were obtained, suggesting that these parameters are not critical. In electromobility shift assays, a p50-containing NF-kappa B nuclear factor from TNF-treated cells binds kappa B-containing probes, and ISGF-2 from IFN-gamma-treated cells binds ICS-containing probes. A probe containing both the kappa B and ICS elements (kappa B-ICS) forms a novel complex with nuclear factors isolated from cells treated with both TNF and IFN-gamma; this complex also forms when nuclear factors from individually cytokine-treated cells are mixed in vitro. The natural variant ICS found in HLA-A responds to IFN-gamma and can mediate synergy with TNF. However, the variant kappa B found in HLA-C does not respond to TNF, nor can it mediate synergy between TNF and IFN-gamma. These observations suggest that synergy between TNF and IFNs in the induction of HLA class I gene expression results from the sum of individual interactions of cytokine-activated enhancer-binding factors with the transcription initiation complex.

IDDM in BB rats. Enhanced MHC class I heavy-chain gene expression in pancreatic islets

Diabetes ◽  
1988 ◽  
Vol 37 (10) ◽  
pp. 1411-1418 ◽  
Author(s):  
S. J. Ono ◽  
B. Issa-Chergui ◽  
E. Colle ◽  
R. D. Guttmann ◽  
T. A. Seemayer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Islets ◽  
Mhc Class I ◽  
Heavy Chain ◽  
Class I ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Bb Rats

Combined treatment with interferon (IFN)-γ and tumor necrosis factor (TNF)-α up-regulates the expression of HLA class I determinants in Burkitt lymphoma lines

1988 ◽  
Vol 117 (2) ◽  
pp. 303-311 ◽  
Author(s):  
Javier Avila-Carin̄o ◽  
Sigurbjörg Torsteinsdottir ◽  
Maria T. Bejarano ◽  
George Klein ◽  
Eva Klein ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Burkitt Lymphoma ◽  
Tumor Necrosis ◽  
Combined Treatment ◽  
Hla Class I ◽  
Class I ◽  
Tnf Α ◽  
Ifn Γ ◽  
Necrosis Factor

Synergistic induction of HLA class I expression by RelA and CIITA

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3804-3808 ◽  
Author(s):  
John Girdlestone
Keyword(s):  
Transcription Factors ◽  
Mhc Class I ◽  
Hla Class I ◽  
Class Ii ◽  
Class I ◽  
Promoter Elements ◽  
Cooperative Action ◽  
Histocompatibility Complex ◽  
Synergistic Induction ◽  
Necrosis Factor

The major histocompatibility complex (MHC) class I genes are induced synergistically by interferons (IFN) and tumor necrosis factor (TNF) , a response thought to involve the cooperative action of Rel/NF-kB and interferon regulatory factor (IRF) transcription factors. The IFN-γ–inducible class II transcriptional activator (CIITA) has recently been shown to transactivate MHC class I as well as class II genes, and this investigation shows that CIITA synergizes strongly with RelA to stimulate HLA class I expression. The functional interaction of CIITA and RelA requires both promoter elements and the upstream Rel binding site and is not seen with a class II reporter. The promoter elements necessary for CIITA action are also required for induction by IFN-. HLA-A and HLA-B loci respond differentially to IFNs, and we identify locus-specific differences in critical promoter elements in addition to known polymorphisms in the Rel and IRF binding sites. The HLA-A promoter is transactivated relatively poorly by CIITA and does not interact detectably with CREB proteins implicated in CIITA recruitment, but the synergism with RelA can compensate for this weakness. The present findings illustrate that multiple transcription factors cooperate to regulate class I expression and that their relative importance differs according to the locus and cell type examined.

scholarly journals Nuclear factors binding to the human immunoglobulin heavy-chain gene enhancer

1987 ◽  
Vol 15 (7) ◽  
pp. 2851-2869 ◽  
Author(s):  
Hiroaki Maeda ◽  
Kazuo Araki ◽  
Daisuke Kitamura ◽  
Jiyang Wang ◽  
Takeshi Watanabe
Keyword(s):  
Heavy Chain ◽  
Immunoglobulin Heavy Chain ◽  
Human Immunoglobulin ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Immunoglobulin Heavy Chain Gene ◽  
Nuclear Factors ◽  
Gene Enhancer ◽  
Heavy Chain Gene Enhancer

Synergistic induction of HLA class I expression by RelA and CIITA

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3804-3808 ◽  
Author(s):  
John Girdlestone
Keyword(s):  
Transcription Factors ◽  
Mhc Class I ◽  
Hla Class I ◽  
Class Ii ◽  
Class I ◽  
Promoter Elements ◽  
Cooperative Action ◽  
Histocompatibility Complex ◽  
Synergistic Induction ◽  
Necrosis Factor

Abstract The major histocompatibility complex (MHC) class I genes are induced synergistically by interferons (IFN) and tumor necrosis factor (TNF) , a response thought to involve the cooperative action of Rel/NF-kB and interferon regulatory factor (IRF) transcription factors. The IFN-γ–inducible class II transcriptional activator (CIITA) has recently been shown to transactivate MHC class I as well as class II genes, and this investigation shows that CIITA synergizes strongly with RelA to stimulate HLA class I expression. The functional interaction of CIITA and RelA requires both promoter elements and the upstream Rel binding site and is not seen with a class II reporter. The promoter elements necessary for CIITA action are also required for induction by IFN-. HLA-A and HLA-B loci respond differentially to IFNs, and we identify locus-specific differences in critical promoter elements in addition to known polymorphisms in the Rel and IRF binding sites. The HLA-A promoter is transactivated relatively poorly by CIITA and does not interact detectably with CREB proteins implicated in CIITA recruitment, but the synergism with RelA can compensate for this weakness. The present findings illustrate that multiple transcription factors cooperate to regulate class I expression and that their relative importance differs according to the locus and cell type examined.

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