Repression of the murine interferon α11 gene: identification of negatively acting sequences

Civas, Ahmet; Dion, Michel; Vodjdani, Guilane; Doly, Janine

doi:10.1093/nar/19.16.4497

Cited by 18 publications

(35 citation statements)

References 33 publications

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“…L929 cells were glycerol shocked with 10% glycerol for 1 min. Virus induction was carried out with Newcastle disease virus (NDV) as previously described (9). Mock-induced cells were treated as described above except that no NDV was added.…”

Section: Methodsmentioning

confidence: 99%

Specific Binding of High-Mobility-Group I (HMGI) Protein and Histone H1 to the Upstream AT-Rich Region of the Murine Beta Interferon Promoter: HMGI Protein Acts as a Potential Antirepressor of the Promoter

Bonnefoy

Bandu

Doly

1999

Molecular and Cellular Biology

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The high-mobility-group I (HMGI) protein is a nonhistone component of active chromatin. In this work, we demonstrate that HMGI protein specifically binds to the AT-rich region of the murine beta interferon (IFN-␤) promoter localized upstream of the murine virus-responsive element (VRE). Contrary to what has been described for the human promoter, HMGI protein did not specifically bind to the VRE of the murine IFN-␤ promoter. Stably transfected promoters carrying mutations on this HMGI binding site displayed delayed virusinduced kinetics of transcription. When integrated into chromatin, the mutated promoter remained repressed and never reached normal transcriptional activity. Such a phenomenon was not observed with transiently transfected promoters upon which chromatin was only partially reconstituted. Using UV footprinting, we show that the upstream AT-rich sequences of the murine IFN-␤ promoter constitute a preferential binding region for histone H1. Transfection with a plasmid carrying scaffold attachment regions as well as incubation with distamycin led to the derepression of the IFN-␤ promoter stably integrated into chromatin. In vitro, HMGI protein was able to displace histone H1 from the upstream AT-rich region of the wild-type promoter but not from the promoter carrying mutations on the upstream high-affinity HMGI binding site. Our results suggest that the binding of histone H1 to the upstream AT-rich region of the promoter might be partly responsible for the constitutive repression of the promoter. The displacement by HMGI protein of histone H1 could help to convert the IFN-␤ promoter from a repressed to an active state.

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Section: Methodsmentioning

confidence: 99%

Specific Binding of High-Mobility-Group I (HMGI) Protein and Histone H1 to the Upstream AT-Rich Region of the Murine Beta Interferon Promoter: HMGI Protein Acts as a Potential Antirepressor of the Promoter

Bonnefoy

Bandu

Doly

1999

Molecular and Cellular Biology

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“…The immediate cellular response to virus infection is characterized by the transcriptional activation of type I IFN 4 genes involved in the host antiviral defense program (1). Multiple IFN-A gene family members are differentially expressed in cultured cells or embryonic fibroblasts infected by virus (2)(3)(4), and in vivo studies indicate that the virus species as well as the natural route of infection determines the magnitude of type I IFN production and the nature of the producer cell.…”

Section: Virus-induced Expression Of Interferon (Ifn)mentioning

confidence: 99%

“…Multiple IFN-A gene family members are differentially expressed in cultured cells or embryonic fibroblasts infected by virus (2)(3)(4), and in vivo studies indicate that the virus species as well as the natural route of infection determines the magnitude of type I IFN production and the nature of the producer cell. For example, plasmacytoid dendritic cells are identified as the major IFN␣/␤-producing cells that rapidly express high levels of IFN-A during systemic infection and acute viremia, whereas local viral infections stimulate delayed and lower IFN-A expression, requiring a positive feedback amplification mechanism dependent on IFN-␤ production in cell types other than IFN␣/␤-producing cells (5)(6)(7)(8).…”

Section: Virus-induced Expression Of Interferon (Ifn)mentioning

confidence: 99%

Promoter Organization of the Interferon-A Genes Differentially Affects Virus-induced Expression and Responsiveness to TBK1 and IKK∈

Civas

Génin

Morin

et al. 2006

Journal of Biological Chemistry

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“…The human sequence used also contains domains similar to the AFI binding site implicated as being involved in the induction of the IFN A4 gene [27], although probably in concert with IRF-1 as this site binds protein identically in both infected and uninfected cells. A third regulatory domain, the TG element, was identified in the murine IFN A4 and A l l genes [28], and this is conserved in human and murine IFN A genes. The overlap in consensus binding sites suggests that there are consequent overlaps in the regulation of the mouse and human IFN A genes, and it is possible that this may extend to mechanisms of tissue-specific activation.…”

Section: Discussionmentioning

confidence: 99%

“…We show that sequences present in the IFN A1 enhancer confer negative regulation on expression of a reporter gene. Negative regulation appears to be important in the regulation of interferon genes, and sequences have been characterized in the murine IFN A l l gene [28,371, and human IFN B 138, 391 and IFN G [C] genes. Our work is discussed with reference to these sequences.…”

mentioning

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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Repression of the murine interferon α11 gene: identification of negatively acting sequences

Cited by 18 publications

References 33 publications

Specific Binding of High-Mobility-Group I (HMGI) Protein and Histone H1 to the Upstream AT-Rich Region of the Murine Beta Interferon Promoter: HMGI Protein Acts as a Potential Antirepressor of the Promoter

Specific Binding of High-Mobility-Group I (HMGI) Protein and Histone H1 to the Upstream AT-Rich Region of the Murine Beta Interferon Promoter: HMGI Protein Acts as a Potential Antirepressor of the Promoter

Promoter Organization of the Interferon-A Genes Differentially Affects Virus-induced Expression and Responsiveness to TBK1 and IKK∈

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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