Differential regulation of HLA class I genes by interferon

Schmidt, Helmut; Gekeler, Volker; Haas, Hubertus; Engler-Blum, G.; Steiert, I.; Probst, Hans; Müller, Claudia

doi:10.1007/bf00204896

Cited by 41 publications

(30 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, HLA-B7 transgenes with 0.66 kb of 5' DNA that were used in our previous studies and found to be expressed appropriately in transgenic animals contained all three of these elements. Additional transfection studies have suggested that regulatory elements also lie 3' to the transcription start site (14,23,33,44).…”

Section: Resultsmentioning

confidence: 99%

“…Additional studies indicate the possibility that regulatory mechanisms involving sequences 3' of the transcription start site also exist (14,23,33,44). Adjacent to one of the enhancers in the 5'-flanking region (enhancer A [20,21] or class I regulatory element [CRE] [7,35]) is a sequence of about 30 bp (the IFN response/consensus sequence [IRS/ ICS]) which was initially identified as being conserved among a number of genes inducible by IFN-ot (13).…”

Section: * Corresponding Authormentioning

confidence: 99%

See 1 more Smart Citation

Identification of cis sequences controlling efficient position-independent tissue-specific expression of human major histocompatibility complex class I genes in transgenic mice.

Chamberlain¹,

Vasavada²,

Ganguly³

et al. 1991

Mol. Cell. Biol.

View full text Add to dashboard Cite

We previously reported that genomic major histocompatibility complex class I human leukocyte antigen (HLA)-B7 gene constructs with as little as 0.66 kb of 5'-and 2.0 kb of 3'-flanking DNA were expressed efficiently and appropriately in transgenic mice. To identify and characterize the relevant cis-acting regulatory elements in more detail, we have generated and analyzed a series of transgenic mice carrying native HLA-B7 genes with further 5' truncations or intronic deletions and hybrid constructs linking the 5'-flanking region of B7 to a reporter gene. We were unable to detect a specific requirement for sequence information within introns 2 to 7 for either appropriate constitutive or inducible class I expression in adult animals. The results revealed the presence of cis-acting regulatory sequences between -0.075 kb and -0.66 kb involved in driving efficient copy number-dependent constitutive and gamma interferon-enhanced tissue-specific expression. The region from -0.11 to -0.66 kb is also sufficient to prevent integration site-specific "position effects," because in its absence HLA-B7 expression is frequently detected at significant levels at inappropriate sites. Conserved sequence elements homologous to the H-2 class I regulatory element, or enhancer A, and the interferon response sequence are located between about -151 and -228 bp of the B7 gene. Our results also indicate the existence of sequences downstream of -0.11 kb which can influence the pattern of tissue-specific expression of the HLA-B7 gene and the ability of this gene to respond to gamma interferon.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: * Corresponding Authormentioning

confidence: 99%

Identification of cis sequences controlling efficient position-independent tissue-specific expression of human major histocompatibility complex class I genes in transgenic mice.

Chamberlain¹,

Vasavada²,

Ganguly³

et al. 1991

Mol. Cell. Biol.

View full text Add to dashboard Cite

show abstract

“…Therefore, it is possible that the IRE functions by enhancing splicing efficiency at the terminal 3Ј splice site, enhancing nuclear to cytoplasmic RNA transport, or by stabilizing nuclear pre-mRNA. The splice junction contained within the 3Ј IRE contains a 5Ј polypyrimidine tract flanking the splice acceptor site (52) and a potential purine-rich exonic splicing enhancer (53,54), raising the possibility that the IRE functions to enhance splicing of the terminal 3Ј exon and, in turn, facilitates nuclear-cytoplasmic mRNA transport (56,57).…”

Section: Discussionmentioning

confidence: 99%

“…Other class I genes, such as HLA-B7 and the murine H-2L and H-2K genes, have been shown to have a functional ISRE region which, by itself, can mediate a strong transcriptional response to IFN-␥ most likely involving the Janus kinase (Jak)/Stat family of protein kinases (18,57). In addition, transcription of the class Ib gene HLA-E has been shown to be stimulated by IFN-␥ through a unique IFN response element, the interferon response region, through the Jak/Stat pathway (58).…”

Section: Discussionmentioning

confidence: 99%

A 3′-Transcribed Region of the HLA-A2 Gene Mediates Posttranscriptional Stimulation by IFN-γ

Snyder

Waring

Sheng

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

The expression of several MHC class I genes is up-regulated at the transcriptional level by IFN-γ. Posttranscriptional mechanisms also have been implicated, but not well characterized. To investigate the mechanism of IFN-γ stimulation of the human MHC class I gene HLA-A2, several human tumor cell lines were transfected with reporter gene constructs driven by the HLA-A2 promoter. We have previously shown that the extended 525-bp HLA-A2 promoter alone, which includes a 5′ IFN-stimulated response element consensus sequence, is not sufficient for IFN-γ response in either K562 or Jurkat cells. In the current study, stable transfection of a genomic HLA-A2 gene construct, containing both 5′- and 3′-flanking sequences, resulted in stimulation of the gene by IFN-γ. Nuclear run-on assays revealed that, unlike other class I genes, IFN-γ stimulation of HLA-A mRNA accumulation occurs almost entirely through posttranscriptional mechanisms. RNA stability assays showed that the effect is not mediated by alteration of the half-life of the HLA-A2 mRNA. Formation of the 3′ end was unaffected by IFN-γ treatment. Sequences that mediate the majority of IFN-γ induction of HLA-A2 mRNA reside in a 127-bp 3′-transcribed region of the gene. This region contains the terminal splice site, the usage of which is not affected by IFN-γ treatment. These results demonstrate a novel posttranscriptional mechanism of regulation of MHC class I genes by IFN-γ.

show abstract

“…Thirteen of these were found to contain the identical sequence that serves as a target for H-2 BF1 and activates transcription in the mouse; five of these have been shown to be functional (Table I). Of the 11 that do not contain the sequence, two are pseudogenes (38 -40), two are HLA-A genes (41,42), two are non-HLA-A/B/C genes that resemble the H-2 TLa/Qa genes of the mouse (43,44), and the final five have been shown to be functional class I genes (45)(46)(47). The isolates of HLA-E and HLA-Aw24 are apparently functional in the thymus (42,43).…”

Section: The H-2 Bf1 Binding Site Is Present 5ј Of Mhc Class I Genes mentioning

confidence: 99%

Activation Transcription Factor 1 Involvement in the Regulation of Murine H-2D Expression

Ishiguro

Brown

Meruelo

1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

Resistance to radiation leukemia virus-induced leukemia is correlated with an increase in H-2D expression on the thymocyte surface. Recently, it has been shown that elevated H-2D d expression on the infected thymocyte is a result of elevated mRNA transcription and that the transcriptional increase is correlated with elevated levels of a DNA binding activity, H-2 binding factor 1 (H-2 BF1), which recognizes the 5 -flanking sequences (5 -TGACGCG-3 ) of the H-2D d gene. This target for transcription factor binding has been found to be identical in the 5 -regulatory region of 12 rodent class I genes, nine of which have been shown to be functional genes. Furthermore, this cis-element is found 5 of 20 primate class I genes (15 human genes), seven of which are known to be functional. Here, we demonstrate that activation transcription factor 1 (ATF-1) is one component of H-2 BF1. In addition, the levels of ATF-1 mRNA in uninfected and radiation leukemia virus-infected thymocytes parallel those of H-2D d mRNA, and therefore, it is suggested that ATF-1 up-regulates the transcription of the H-2D d gene after radiation leukemia virus infection of thymocytes. Transfection experiments also demonstrate that ATF-1 activates a reporter plasmid that contains the H-2 BF1 motif, but not a reporter lacking this motif. This is the first demonstration of the interaction of ATF-1 with 5 -regulatory sequences of major histocompatibility complex class I genes.

show abstract

Differential regulation of HLA class I genes by interferon

Cited by 41 publications

References 43 publications

Identification of cis sequences controlling efficient position-independent tissue-specific expression of human major histocompatibility complex class I genes in transgenic mice.

Identification of cis sequences controlling efficient position-independent tissue-specific expression of human major histocompatibility complex class I genes in transgenic mice.

A 3′-Transcribed Region of the HLA-A2 Gene Mediates Posttranscriptional Stimulation by IFN-γ

Activation Transcription Factor 1 Involvement in the Regulation of Murine H-2D Expression

Contact Info

Product

Resources

About