The human β-interferon gene enhancer is under negative control

Goodbourn, Stephen; Burstein, Hal; Maniatis, Tom

doi:10.1016/0092-8674(86)90292-8

Cited by 405 publications

(207 citation statements)

References 40 publications

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“…In fact, postinduction repression of the IFN-␤ gene has been shown to be mediated by a non-IRF family protein, PRDI-BF1, which binds to the IFN-␤ PRDI element (26), and perhaps also by the binding of homodimers of the rel family protein p50 to the PRDII element (83). Constitutive repression of the IFN-␤ gene is believed to be mediated by the binding of an unidentified factor to a region which overlaps the PRDII domain (but not the PRDI-ICS site) (15,16). IRF2 is thus not responsible for the repression of transcription from the IFN genes, and it does not contribute to the postinduction decrease in IFN gene transcription.…”

Section: Discussionmentioning

confidence: 99%

Constitutive Activation of Epstein-Barr Virus (EBV) Nuclear Antigen 1 Gene Transcription by IRF1 and IRF2 during Restricted EBV Latency

Schaefer

Paulson

Strominger

et al. 1997

Molecular and Cellular Biology

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Epstein-Barr virus (EBV) infection in immunocompetenthumans is predominantly latent and persists for the life of the individual (reviewed in reference 41). Recently, it has been shown that EBV is capable of adopting at least three distinct forms of latency (27). Type III latency is observed upon in vitro infection of B lymphocytes and results in immortalization and continuous proliferation of the infected B cells via the action of a subset of the six EBV nuclear antigens (EBNAs; EBNA1, EBNA2, EBNA3a, EBNA3b, EBNA3c, and EBNA4) and three membrane proteins (LMP1, LMP2a, and LMP2b) expressed in the type III (immortalizing) program. However, in vivo, the type III latency program is likely to be only transiently observed upon initial infection of a naive host, since several of the type III latent antigens elicit a potent cytotoxic T-lymphocyte response resulting in very effective elimination of type III latently infected B cells (reviewed in reference 33).EBV is also capable of entering programs of latency in which the expression of latent antigens is restricted with respect to the type III program. In type I latency, only the EBNA1 protein is expressed (64). It has recently been shown that EBNA1 peptides do not enter the major histocompatibility complex class I antigen processing and presentation pathway (29, 39, 52), and cells which express only EBNA1 are not detected by host cellular immune surveillance mechanisms (63). The type II latency program differs from type I latency only in the expression of variable combinations of LMP1, LMP2a, and LMP2b, in addition to EBNA1. Since the type I latency program was identified, there has been speculation that type I latently infected B lymphocytes represent the lifelong reservoir of virus in immunocompetent, seropositive individuals, and there have recently been several reports which provide evidence that a type I-like form of restricted viral latency does indeed exist in healthy carriers of EBV (6,51,60,85).Investigations into the molecular basis of type III and type I latency have demonstrated that distinct promoters are used to drive transcription of the EBNAs in each latent program. In type III latency, transcription of all six nuclear antigens is initiated from either Wp (during initial infection of resting B cells) or Cp (in cycling B cells), and the long primary transcripts are differentially spliced to generate the mature EBNA transcripts (75, 94; see Fig. 1A for a schematic representation of EBV latent transcription and locations of promoters). Recent investigations have shown that transcription of the EBNA1 gene in type I latency is driven by a promoter designated Qp, which is considerably downstream of the type III latency EBNA gene promoters (57,(70)(71)(72). Qp has an architecture with numerous similarities to eukaryotic housekeeping

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Section: Discussionmentioning

confidence: 99%

Constitutive Activation of Epstein-Barr Virus (EBV) Nuclear Antigen 1 Gene Transcription by IRF1 and IRF2 during Restricted EBV Latency

Schaefer

Paulson

Strominger

et al. 1997

Molecular and Cellular Biology

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“…In addition, negative regulation of the enhancer is also an important mechanism for the control of heavy-chain expression. Negative-enhancer regulation may be a general mechanism for tissue-specific expression as negativeregulatory elements also have been found that are associated with the insulin 1 gene enhancer (Laimins et al 1986;Nit et al 1986), the B-interferon gene enhancer {Goodbourn et al 1986), and viral enhancers in embryonic stem cells (Gorman et al 1985), and mouse mammary epithelial cells (Langer and Ostrowski 1988).…”

Section: Models For Enhancer Repressionmentioning

confidence: 99%

A developmental-specific factor binds to suppressor sites flanking the immunoglobulin heavy-chain enhancer.

Scheuermann¹,

Chen²

1989

Genes Dev.

108

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We identified a novel nuclear protein, NF-|jiNR, that binds to multiple sites flanking the immunoglobulin heavy-chain enhancer. The expression of NF-|jiNR shows a unique developmental pattern; the activity is present in all cells representing early stages of B-cell development, but is absent from more mature cells that express a high level of immunoglobulin heavy chains. NF-|iNR also is present in most cell lines outside of the B-cell lineage (e.g., T cells, macrophages, and fibroblasts). The binding sites for NF-|jiNR correlate very well with cisacting negative regulatory elements of the heavy-chain enhancer defined previously. Indeed, when the segments bound by NF-^.NR are deleted from the enhancer, it is now found to function as a positive transcription element in T cells and macrophages. Taken together, these results suggest that NF-|jiNR may function as a negative regulator of enhancer function. The observation that the segments bound by NF-ftNR correspond to the segments bound to the nuclear matrix suggests an intriguing model not only of how enhancers might function but also of how negative regulation might occur.

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“…This region of the human promoter contains seven copies of repetitive hexanucleotide sequences, certain copies of which have been shown to confer virus inducibility upon a reporter gene when present as a four-to eight-copy tandem repeat (13). Two positive regulatory domains have been defined within this region, PRD-I between positions -77 and -64 and PRD-II between positions -66 and -55 (16). Part of this region between positions -91 and -64 shows considerable homology with elements, particularly with the IFN-responsive sequence present within the flanking region of a number of unrelated genes, the expression of which is regulated by IFN (18,20,21,26,34).…”

mentioning

confidence: 99%

Priming affects the activity of a specific region of the promoter of the human beta interferon gene.

Dron¹,

Lacasa²,

Tovey³

1990

Mol. Cell. Biol.

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Treatment of Daudi or HeLa cells with human interferon (IFN) alpha 8 before induction with either poly(I)-poly(C) or Sendai virus resulted in an 8- to 100-fold increase in IFN production. The extent of priming in Daudi cells paralleled the increase in the intracellular content of IFN-beta mRNA. IFN-alpha mRNA remained undetectable in poly(I)-poly(C)-treated Daudi cells either before or after priming. An IFN-resistant clone of Daudi cells was found to produce 4- to 20-fold more IFN after priming, indicating that priming was unrelated to the phenotype of IFN sensitivity. IFN treatment of either Daudi or HeLa cells transfected with the human IFN-beta promoter (-282 to -37) linked to the chloramphenicol acetyltransferase (CAT) gene resulted in an increase in CAT activity after induction with poly(I)-poly(C) or Sendai virus. A synthetic double-stranded oligonucleotide corresponding to an authentic 30-base-pair (bp) region of the human IFN-beta promoter between positions -91 and -62 was found to confer virus inducibility upon the reporter CAT gene in HeLa cells. IFN treatment of HeLa cells transfected with this 30-bp region of the IFN-beta promoter in either the correct or reversed orientation also increased CAT activity upon subsequent induction. IFN treatment alone had no detectable effect on the activity of either the 30-bp region or the complete human IFN promoter.

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The human β-interferon gene enhancer is under negative control

Cited by 405 publications

References 40 publications

Constitutive Activation of Epstein-Barr Virus (EBV) Nuclear Antigen 1 Gene Transcription by IRF1 and IRF2 during Restricted EBV Latency

Constitutive Activation of Epstein-Barr Virus (EBV) Nuclear Antigen 1 Gene Transcription by IRF1 and IRF2 during Restricted EBV Latency

A developmental-specific factor binds to suppressor sites flanking the immunoglobulin heavy-chain enhancer.

Priming affects the activity of a specific region of the promoter of the human beta interferon gene.

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