Virus induction of human IFNβ gene expression requires the assembly of an enhanceosome

Thanos, Dimitris; Maniatis, Tom

doi:10.1016/0092-8674(95)90136-1

Cited by 939 publications

(822 citation statements)

References 45 publications

Supporting

Mentioning

780

Contrasting

Unclassified

Order By: Relevance

“…These proteins bind the minor groove of AT-rich DNA sequences through three short basic repeats, called 'AT-hooks', located at the NH2-terminal region of the proteins. The mammalian HMGA proteins play key roles in chromatin architecture and gene control by serving as generalized chromatin effectors, either enhancing or suppressing the ability of most usual transcriptional activators and repressors to act within the confines of chromatinized DNA (Reeves and Nissen, 1990;Thanos and Maniatis, 1995).…”

Section: Introductionmentioning

confidence: 99%

Regulation of microRNA expression by HMGA1 proteins

et al. 2009

View full text Add to dashboard Cite

The High Mobility Group proteins HMGA1 are nuclear architectural factors that play a critical role in a wide range of biological processes. Since recent studies have identified the microRNAs (miRNAs) as important regulators of gene expression, modulating critical cellular functions such as proliferation, apoptosis and differentiation, the aim of our work was to identify the miRNAs that are physiologically regulated by HMGA1 proteins. To this purpose, we have analysed the miRNA expression profile of mouse embryonic fibroblasts (MEFs) carrying two, one or no Hmga1 functional alleles using a microarray (miRNA microarray). By this approach, we found a miRNA expression profile that differentiates Hmga1-null MEFs from the wild-type ones. In particular, a significant decrease in miR-196a-2, miR-101b, miR-331 and miR-29a was detected in homozygous Hmga1-knockout MEFs in comparison with wild-type cells. Consistently, these miRNAs are downregulated in most of the analysed tissues of Hmga1-null mice in comparison with the wild-type mice. ChIP assay shows that HMGA1 is able to bind regions upstream of these miRNAs. Moreover, we identified the HMGA2 gene product as a putative target of miR-196a-2, suggesting that HMGA1 proteins are able to downregulate the expression of the other member of the HMGA family through the regulation of the miR-196a-2 expression. Finally, ATXN1 and STC1 gene products have been identified as targets of miR-101b. Therefore, it is reasonable to hypothesize that HMGA1 proteins are involved in several functions by regulating miRNA expression.

show abstract

Section: Introductionmentioning

confidence: 99%

Regulation of microRNA expression by HMGA1 proteins

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Expression of these genes is regulated primarily at the transcriptional level, and numerous studies have identified cis-acting DNA elements and transcription factors which regulate these genes. In particular, much attention has been focused on the DNA elements which function as virus-inducible enhancers; these elements include sequences such as GAAAACT-GAAAGG and GAGAAGTGAAAGT in the human IFN-b gene promoter Thanos & Maniatis 1995) and GAAAGCAAAACA in the human IFN-a1 gene (MacDonald et al 1990). In addition, several transcription factors which bind to the 5 0 -regulatory regions of these genes have been described, including TG factor, NF-kB, ATF-2 H Harada et al…”

Section: Introductionmentioning

confidence: 99%

“…and HMG-I(Y) (MacDonald et al 1990;Sen & Ranshoff 1993;Taniguchi et al 1995;Thanos & Maniatis 1995).…”

Section: Introductionmentioning

confidence: 99%

Regulation of IFN‐α/β genes: evidence for a dual function of the transcription factor complex ISGF3 in the production and action of IFN‐α/β

et al. 1996

View full text Add to dashboard Cite

“…In addition, our data suggest that FOXO3 could also inhibit IFN-λ1 transcription, a type III IFN also involved in innate antiviral immunity [32]. Thus, it is possible that FOXO3 may play a larger role in controlling antiviral activity of DCs than originally suspected, but the physiological relevance of this inhibitory effect remains to be demonstrated.IFN-β production in response to TLR3/4 stimulation is initiated through the coordinated activation of a set of transcription factors including NF-κB and IRFs [30,33]. Our results suggest that FOXO3 may affect expression of IFN-β via inhibition of both transcription factors.…”

mentioning

confidence: 69%

FOXO3 as a new IKK‐ε‐controlled check‐point of regulation of IFN‐β expression

et al. 2012

View full text Add to dashboard Cite

Cell survival transcription factor FOXO3 has been recently implicated in moderating proinflammatory cytokine production by dendritic cells (DCs), but the molecular mechanisms are unclear. It was suggested that FOXO3 could antagonize NF-κB activity, while IKK-β was demonstrated to inactivate FOXO3, suggesting a cross-talk between the two pathways. Therefore, FOXO3 activity must be tightly regulated to allow for an appropriate inflammatory response. Here, we show that in human monocyte-derived DCs (MDDCs), FOXO3 is able to antagonize signaling intermediates downstream of the Toll-like receptor (TLR) 4, such as NF-κB and interferon regulatory factors (IRFs), resulting in inhibition of interferon (IFN)-β expression.We also demonstrate that the activity of FOXO3 itself is regulated by IKK-ε, a kinase involved in IFN-β production, which phosphorylates and inactivates FOXO3 in response to TLR4 agonists. Thus, we identify FOXO3 as a new IKK-ε-controlled check-point of IRF activation and regulation of IFN-β expression, providing new insight into the role of FOXO3 in immune response control.Keywords: Activation-induced cell death r Cell volume regulation r T-cell response r Taurine transporter Supporting Information available online IntroductionThe FOXO transcription factors (FOXO1, FOXO3, FOXO4, and FOXO6) are involved in a wide range of cellular processes including cell-cycle arrest, apoptosis, oxidative stress detoxification, and cellular homeostasis [1][2][3]. Given their importance in such critical cellular functions, their activity is tightly regulated by posttranslational modifications, mainly via the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway [4]. In response to growth factors or cytokines, FOXO proteins are phosphorylated by AKT Correspondence: Dr. Lionel Luron e-mail: luron@ciml.univ-mrs.fr at three conserved serine/threonine residues (Thr 32 , Ser 253 , and Ser 315 of FOXO3) resulting in the protein inactivation via nuclear exclusion and subsequent degradation [5,6].More recently, FOXO factors have been shown to play a role in immunity and inflammation [7][8][9][10][11]. In addition to their critical role in homeostasis of immune-relevant cells including B and T cells [7][8][9], FOXOs are associated with inflammatory diseases [12,13]. Moreover, FOXO3 was identified as a key factor in regulation of the innate immune response [10]. In FOXO3-deficient mice, production of major proinflammatory cytokines IL-6 and TNF-α by dendritic cells (DCs) is increased in response to viral infection, resulting in a greater expansion of T-cell population [10]. Expression of proinflammatory cytokines as well as type I interferons (IFNs) in response to viral and microbial stimuli is regulated by a number of key transcription factors, including NF-κB and [20,21]. Interestingly, its overexpression in a breast cancer model system could functionally replace PI3K constitutive activation and prevent cell-cycle arrest and apoptosis [20], processes often mediated by FOXO3 target genes, such as Cyclin D, p27/KIP1, FasL, bim...

show abstract

Virus induction of human IFNβ gene expression requires the assembly of an enhanceosome

Cited by 939 publications

References 45 publications

Regulation of microRNA expression by HMGA1 proteins

Regulation of microRNA expression by HMGA1 proteins

Regulation of IFN‐α/β genes: evidence for a dual function of the transcription factor complex ISGF3 in the production and action of IFN‐α/β

FOXO3 as a new IKK‐ε‐controlled check‐point of regulation of IFN‐β expression

Contact Info

Product

Resources

About