Reversible silencing of enhancers by sequences derived from the human IFN-α promoter

Kuhl, Dietmar; Fuente, José de la; Chaturvedi, Madan M.; Parimoo, Satish; Ryals, John; Meyer, François; Weissmann, Charles

doi:10.1016/0092-8674(87)90172-3

Cited by 118 publications

(77 citation statements)

References 58 publications

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“…This mechanism has been proposed to explain silencer activity at the mating-type locus in yeast (Brand et al 1985), the silencing of the SV40 enhancer by multimerized PRDI in mammalian cells {Kuhl et al 1987), and the negative regulatory activity of the Drosophila zinc-finger protein Krfippel (Licht et al 1990). In the case of Krfippel, a region of the protein that does not include the zinc fingers is both necessary and sufficient to confer repression activity to another DNA-binding protein (Licht et al 1990).…”

Section: Mechanism Of Repression By Prdi-bf1mentioning

confidence: 99%

“…PRDI differs by only one nucleotide from the interferon-stimulated response element {ISRE}, an element required for induction of a number of genes by IFN {Levy et al 1988;Fan and Maniatis 1989). PRDI is necessary for the induction of the I3-IFN gene and is sufficient when multimerized to confer both virus {Fujita et al 1987;Kuhl et al 1987;Maniatis 1989} andIFN {Fan andManiatis 1989;MacDonald et al 1990) inducibility to a heterologous promoter. Virus induction of synthetic promoters containing multipie PRDI sites occurs with the same kinetics as the intact [3-IFN gene promoter, and the postinduction tumoff also requires protein synthesis [Whittemore and Maniatis 1990bl.…”

mentioning

confidence: 99%

“…Thus, PRDI can function as both a positive and negative regulatory element at different times after induction. These observations suggest that PRDI-dependent virus induction requires the activation of a preexisting transcription factor, whereas postinduction repression requires the synthesis of a repressor [Whittemore and Maniatis 1990bl. Further evidence that PRDI can act as a negative regulatory element is provided by the observation that multiple copies of PRDI can reduce the activity of the SV40 enhancer in some cell types when inserted between the enhancer and the TATA box (Kuhl et al 1987; Fan and Maniatis 1989). This blocking activity is relieved upon virus induction.…”

mentioning

confidence: 99%

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Identification and characterization of a novel repressor of beta-interferon gene expression.

Keller¹,

Maniatis²

1991

Genes Dev.

332

306

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We have identified and characterized a novel repressor of human ~-interferon (13-IFN) gene expression. This protein, designated PRDI-BF1, binds specifically to the PRDI element of the 13-IFN gene promoter and is distinct from previously reported proteins that bind to this sequence. PRDI-BF1 is an 88-kD protein containing five zinc-finger motifs. Cotransfection experiments in cultured mammalian cells revealed that PRDI-BF1 is a potent repressor of PRDI-dependent transcription. PRDI-BF1 blocks virus induction of the intact 13-IFN gene promoter and of synthetic promoters containing multiple PRDI sites. PRDI-BF1 can also block the SV40 enhancer when PRDI sites are located between the enhancer and the promoter. This repression is highly dependent on the location of the PRDI sites, however, indicating that PRDI-BF1 cannot act at a distance. On the basis of the properties of PRDI-BF1 and the observation that PRDI-BF1 mRNA accumulation is virus inducible, we propose that PRDI-BF1 may act as a postinduction repressor of the 13-IFN gene by displacing positive regulatory proteins from the PRDI site of the promoter.[Key Words: Negative control of gene expression; zinc-finger protein~ virus induction]

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Section: Mechanism Of Repression By Prdi-bf1mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Identification and characterization of a novel repressor of beta-interferon gene expression.

Keller¹,

Maniatis²

1991

Genes Dev.

332

306

View full text Add to dashboard Cite

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“…Although the sequenced region of the Pcp-2 gene does not contain known silencer elements (Laimins et al 1986;Nir et al 1986;Baniahmad et al 1987Baniahmad et al , 1990Bouvagnet et al 1987;Imler et al 1987;Kuhl et al 1987;Osborne et al 1988;Berg et al 1989;Burt et al 1989;Cao et al 1989;Emerson et al 1989;Herbst et al 1989;Winoto and Baltimore 1989;Ayer and Benyajati 1990;Farrell et al 1990;Mathey-Prevot et al 1990;Salier et al 1990;Savagner et al 1990), such elements could be specific to the Pcp-2 gene and/or be located in the flanking DNA not yet sequenced.…”

Section: Pcp-2 Expression Has Not Been Observed Other Than Inmentioning

confidence: 99%

Purkinje cell protein-2 regulatory regions and transgene expression in cerebellar compartments.

Vandaele¹,

Nordquist²,

Feddersen³

et al. 1991

Genes Dev.

123

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“…This sequence is similar to the human IFN At VRE in that it contains a consensus binding site for the virus-inducible IRF-1 regulatory protein. This domain has been implicated in negative regulation of the human IFN A1 gene in the absence of virus induction [37]. A construct containing tetrameric copies of repA, a domain containing the IRF-1 binding consensus sequence, was shown to be able to silence transcription from a 72-bp SV40 promoter.…”

Section: Discussionmentioning

confidence: 99%

A Regulatory Domain within the Virus‐Response Element of the Interferon α1 Gene Acts as a Transcriptional Repressor Sequence and Determinant of Cell‐Specific Gene Expression

Dent

Gewert

1996

European Journal of Biochemistry

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Type-I interferons are encoded by a multigene family, the major members of which are at least 13 IFN A subtypes and a single IFN B gene. IFNs A and B are induced in response to similar stimuli, such as virus infection and double-stranded RNA, but in different cell types: the induction of IFN A is almost exclusively restricted to cells of lymphoid origin, while IFN B has been found to be induced in a variety of cell types including fibroblasts. The virus-responsive enhancer element in the promoter region of IFN A family members is largely responsible for the differential expression of individual subtypes in responsive cells. In this paper we describe experiments which address the issue of the differential expression of IFN A and IFN B in different cell types. We show that IFN-P is induced in a variety of cells of different origin, while not all of these are able to secrete IFN-a. By transfection of reporter gene constructs comprising the virus-responsive enhancer from the IFN A1 and IFN B genes, we show that this differential response is mediated at the level of transcription via these control elements. More detailed analysis of the function of these regions identifies specific sequences within the IFN A1 virus response element that has an inhibitory effect on expression in cells that are normally inducible, and is also implicated in the overall suppression of IFN A induction in non-inducible cells.Keywords: interferon ; transcription ; cell specific ; Sendai virus ; repression.The interferons (IFNs) are a family of secreted cytokines induced in mammalian cells in response to a number of stimuli including virus infection (reviewed in [3 -51). The interferon proteins function via a cell surface receptor, and confer antiviral and antiproliferative effects on cells. The interferons are subdivided into two major classes, type I and type 11, on the basis of their immunological and biological properties. These two types are largely unrelated, although they act through an overlapping network of responsive genes. The work in this paper addresses the induction of type-I gene expression. The type-I IFNs are encoded by a multigene family located on chromosome 9 in human cells [6][7][8] (chromosome 4 in mouse) and may be further subdivided into three groups. IFN-a is expressed almost exclusively in cells of lymphoid origin, and consists of several subtypes derived from around 13 functional genes. IFN-P was initially identified as being produced by fibroblast cells [9] and is derived from a single gene. Expression of IFN-/I is more widespread than TFN-a, with most cell types being capable of its secretion. The third identified member of the type I IFN family is trophoblast IFN (IFN-w) Virus induction of the expression of interferons has been demonstrated to occur at the level of gene transcription (reviewed in [12-141), although regulation may also occur at other levels, including that of mRNA instability [I 5, 161. Transcriptional enhancer sequences through which virus induction is mediated have been identified for both hu...

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Reversible silencing of enhancers by sequences derived from the human IFN-α promoter

Cited by 118 publications

References 58 publications

Identification and characterization of a novel repressor of beta-interferon gene expression.

Identification and characterization of a novel repressor of beta-interferon gene expression.

Purkinje cell protein-2 regulatory regions and transgene expression in cerebellar compartments.

A Regulatory Domain within the Virus‐Response Element of the Interferon α1 Gene Acts as a Transcriptional Repressor Sequence and Determinant of Cell‐Specific Gene Expression

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