A transcriptional enhancer and an interferon-responsive sequence in major histocompatibility complex class I genes.

Vogel, J; Kress, M; Khoury, G; Jay, G

doi:10.1128/mcb.6.10.3550

Cited by 49 publications

(23 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This similar sequence was in the opposite orientation, consistent with the enhancerlike capacity of the ISG15 5'-flanking sequence (Reich et al 1987). Other genes known to be strongly induced by IFN, such as 6-16 (Porter et al 1988), C202 ISamanta et al 1986, and H-2 Vogel et al 1986), also contain a strong homology limited to about 15 nucleotides. This region of homology is much smaller, but it is contained within the sequence predicted previously by Friedman and Stark (1985) on the basis of sequence comparison alone for genes whose sequences were known (metallothionine and histocompatibility genes) but whose IFN-responsive regions had not been identified.…”

Section: Genes and Development 385mentioning

confidence: 61%

Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control.

Levy¹,

Kessler²,

Pine³

et al. 1988

Genes Dev.

538

412

View full text Add to dashboard Cite

Human ~-and 13-interferons (IFNs) stimulate rapid but transient increases in transcription from a set of previously quiescent genes. Protein synthesis is not required for initial stimulation, but duration of the response is limited to a few hours by a process requiring synthesis of new proteins. An IFN-stimulated response element (ISRE) was identified 5' to an inducible gene by deletion analysis and point mutagenesis, and sequence comparisons with other promoters defined the consensus element YAGTTTC(A/T)YTTTYCC. Two classes of IFN-inducible nuclear factors were found that bind to the ISRE. The most rapidly induced factor appeared without new protein synthesis, whereas a second factor required active protein synthesis for its appearance and maintenance. The kinetics of appearance and loss of these binding activities correlate with the activation and repression of IFN-stimulated genes. These different IFN-activated or induced factors may bind sequentially to the same essential promoter element to first increase and then repress transcription.

show abstract

Section: Genes and Development 385mentioning

confidence: 61%

Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control.

Levy¹,

Kessler²,

Pine³

et al. 1988

Genes Dev.

538

412

View full text Add to dashboard Cite

show abstract

“…Recently, Vogel et al (43) have shown that the transient expression of a CAT gene directed by 1.9 kb of the 5' flanking region of the H-2Ld gene is not down-regulated in adenovirus type 12-transformed cells, even though the level of transcription of endogenous h-2 genes in these cells is only 5% of the normal cell level. It is possible that the data from this system are analogous to our own data relating to the M-MSV effect on transient expression of a CAT gene directed by 2.1 kb of H-2Kb 5' flanking region.…”

Section: Downloaded Frommentioning

confidence: 99%

Murine retroviruses control class I major histocompatibility antigen gene expression via a trans effect at the transcriptional level.

Wilson¹,

Flyer²,

Faller³

1987

Mol. Cell. Biol.

View full text Add to dashboard Cite

Moloney murine leukemia virus (M-MuLV) and Moloney murine sarcoma virus (M-MSV) exert a regulatory effect on the class I genes of the murine major histocompatibility complex (MHC). We have previously shown that M-MuLV infection of mouse fibroblasts results in a substantial increase in cell surface expression of H-2K, H-2D, and H-2L proteins, whereas M-MSV, upon coinfection of the same cells, is apparently able to override the MuLV-induced increase in H-2 expression. As a result of this modulation, immune recognition of the infected cells is profoundly altered. Our efforts have been directed toward elucidating the molecular basis for this phenomenon. We report here that stimulation of interferon production as a result of infection with MuLV does not occur and, therefore, is not the cause of MuLV-induced enhancement of MHC expression. Control of H-2 class I and 02-microglobulin gene expression by M-MuLV, and probably by M-MSV, takes place at the transcriptional level as indicated by nuclear runoff studies and analysis of steady-state mRNA levels. Our demonstration that M-MuLV controls expression of widely separated endogenous cellular genes (those coding for H-2D, H-2K, H-2L, and (l2-microglobulin), transfected class I MHC genes, and unintegrated chimeric genes consisting of fragments of class I MHC genes linked to sequences encoding a procaryotic enzyme, chloramphenicol acetyltransferase, suggests that M-MuLV exerts its effect in trans and not by proviral integration in the vicinity of the H-2 gene complex. Finally, we show that the sequences of at least one MHC gene, which are responsive to trans regulation by M-MuLV, lie within 1.2 kilobases upstream of the initiation codon for that gene. Class I genes of the H-2 gene complex in mouse, and the HLA complex in humans, encode protein products which are expressed in association with P2-microglobulin on the surfaces of nucleated cells (23). In addition to serving as the target molecules in allogeneic graft rejection, these proteins are essential for the recognition and elimination of neoplastic and virus-infected cells by the cytotoxic T cells (CTLs) of the host immune system (37, 44). The level of expression of H-2 class I proteins on virus-infected cells has been correlated with the degree of effectiveness with which they are destroyed by the CTLs (18, 34). It is, therefore, reasonable to expect that viruses with the capability of altering H-2 expression in the cells they infect may be influencing their own survival.Previously, this laboratory has reported that cells chronically express significantly increased surface levels of H-2K, H-2D, and H-2L proteins after infection with the Moloney murine leukemia virus (M-MuLV) (18). These infected cells are efficiently lysed by M-MuLV-specific CTLs and also by allospecific CTLs, a reflection of their increased level of H-2 class I antigens. Coinfection of cells with M-MuLV and the replication-defective, acutely transforming Moloney murine sarcoma virus (M-MSV) eliminates the H-2 enhancement, as well as profoundly decreas...

show abstract

“…The binding sites on DNA for ISGF3, called IFN-stimulated response elements (ISREs), are found near promoters of most IFN-␣/␤-responsive genes (7,19,31,33,34,48). The ISGF3 transcription factor is an oligomeric protein with three subunits: STAT1, STAT2, and a 48-kDa DNA-binding protein (9,10,38,46).…”

mentioning

confidence: 99%

Role of STAT2 in the Alpha Interferon Signaling Pathway

Leung

Qureshi

Kerr

et al. 1995

Molecular and Cellular Biology

263

216

View full text Add to dashboard Cite

(22,26,43,44), and transcription factor subunits called STATs (signal transducers and activators of transcription) (8, 39). Phosphorylated STATs, which also contain Src homology 2 (SH2) domains, associate to form homo-and heterodimers (40, 51). These dimers, with or without additional cofactors, migrate to the nucleus, where they activate the transcription of IFN-responsive genes (5).IFN-␣ and -␤ induce formation of the transcription factor IFN-stimulated gene factor 3 (ISGF3) (4,20). The binding sites on DNA for ISGF3, called IFN-stimulated response elements (ISREs), are found near promoters of most IFN-␣/␤-responsive genes (7,19,31,33,34,48). The ISGF3 transcription factor is an oligomeric protein with three subunits: STAT1, STAT2, and a 48-kDa DNA-binding protein (9,10,38,46). STAT1 exists in two alternatively spliced forms of 91 kDa (STAT1␣) and 84 kDa (STAT1␤); either is capable of participating in ISGF3 formation (27). STAT2 is a 113-kDa protein having approximately 40% homology with STAT1␣ (10). Unlike IFN-␣/␤, IFN-␥ triggers the phosphorylation on tyrosine of STAT1 but not STAT2 (41), leading to formation of the gamma-activated transcription factor GAF, which binds to the gamma-activated sequences (GAS) (6,21,42). GAF is formed when STAT1␣ subunits dimerize through reciprocal SH2 domain-phosphotyrosine interactions (40). Phosphorylation of STAT1 and formation of STAT1 homodimers can also be activated by IFN-␣. Before the STAT proteins were recognized, this IFN-␣-activated factor was called AAF (6).Unphosphorylated STAT1␣ binds to a specific phosphotyrosine near the C terminus of the IFN-␥ receptor ␣ chain (12). Phosphorylation of this tyrosine upon binding of IFN-␥ to the receptor is an early step in the IFN-␥ signaling pathway, creating a binding site for the unphosphorylated transcription factor subunit in proximity to the receptor-bound tyrosine kinases JAK1 and JAK2 (26, 49). The IFN-␣ receptor may employ a similar mechanism. However, although phosphorylation of the IFN-␣ receptor has been observed (30), the site is not yet known.Genetic studies using mutant cell lines unresponsive to the IFNs (17,24,29,49) have established the functional importance of JAKs and STATs in the pathways. Two JAK family kinases, TYK2 (47) and JAK1 (26), as well as STAT1 (27) and the 48-kDa DNA-binding protein (17) are required for the response of most genes to IFN-␣. However, the situation is somewhat complex in that mutants lacking TYK2 retain a weak response to , probably mediated by formation of ISGF3 (15). Furthermore, some genes (IRF-1, for example) respond to IFN-␣/␤ independently of ISGF3, utilizing AAF to activate a GAS-like element (6, 13). The availability of mutant cell lines lacking the individual proteins of ISGF3 allows analysis of the function of each protein separately. Study of U3A cells, which lack STAT1␣ and -␤, has shown that STAT1␣ (but not STAT1␤) is required in the IFN-␥ pathway, that either STAT1␣ or STAT1␤ can function in the IFN-␣ pathway, and that Y-701 (the phosphorylation site in STAT1) and R...

show abstract

A transcriptional enhancer and an interferon-responsive sequence in major histocompatibility complex class I genes.

Abstract: The major histocompatibility complex class I antigens play an indispensable role in cell-cell interactions.

Cited by 49 publications

References 27 publications

Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control.

Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control.

Murine retroviruses control class I major histocompatibility antigen gene expression via a trans effect at the transcriptional level.

Role of STAT2 in the Alpha Interferon Signaling Pathway

Contact Info

Product

Resources

About