High Dose IFN-β Activates GAF to Enhance Expression of ISGF3 Target Genes in MLE12 Epithelial Cells
Interferon β (IFN-β) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN-β activates a second transcription factor complex, γ-activated factor (GAF), but the signifi...
Ausführliche Beschreibung
Autor*in: |
Kensei Kishimoto [verfasserIn] Catera L. Wilder [verfasserIn] Justin Buchanan [verfasserIn] Minh Nguyen [verfasserIn] Chidera Okeke [verfasserIn] Alexander Hoffmann [verfasserIn] Quen J. Cheng [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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Schlagwörter: |
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Übergeordnetes Werk: |
In: Frontiers in Immunology - Frontiers Media S.A., 2011, 12(2021) |
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Übergeordnetes Werk: |
volume:12 ; year:2021 |
Links: |
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DOI / URN: |
10.3389/fimmu.2021.651254 |
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Katalog-ID: |
DOAJ06890746X |
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520 | |a Interferon β (IFN-β) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN-β activates a second transcription factor complex, γ-activated factor (GAF), but the significance of this coordinated activation is unclear. We report that in murine lung epithelial cells (MLE12) high doses of IFN-β indeed activate both ISGF3 and GAF, which bind to distinct genomic locations defined by their respective DNA sequence motifs. In contrast, low doses of IFN-β preferentially activate ISGF3 but not GAF. Surprisingly, in MLE12 cells GAF binding does not induce nearby gene expression even when strongly bound to the promoter. Yet expression of interferon stimulated genes is enhanced when GAF and ISGF3 are both active compared to ISGF3 alone. We propose that GAF may function as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity and establish pro-inflammatory states. | ||
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10.3389/fimmu.2021.651254 doi (DE-627)DOAJ06890746X (DE-599)DOAJ4989123231dd488dbb9bb4729c3cfccf DE-627 ger DE-627 rakwb eng RC581-607 Kensei Kishimoto verfasserin aut High Dose IFN-β Activates GAF to Enhance Expression of ISGF3 Target Genes in MLE12 Epithelial Cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Interferon β (IFN-β) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN-β activates a second transcription factor complex, γ-activated factor (GAF), but the significance of this coordinated activation is unclear. We report that in murine lung epithelial cells (MLE12) high doses of IFN-β indeed activate both ISGF3 and GAF, which bind to distinct genomic locations defined by their respective DNA sequence motifs. In contrast, low doses of IFN-β preferentially activate ISGF3 but not GAF. Surprisingly, in MLE12 cells GAF binding does not induce nearby gene expression even when strongly bound to the promoter. Yet expression of interferon stimulated genes is enhanced when GAF and ISGF3 are both active compared to ISGF3 alone. We propose that GAF may function as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity and establish pro-inflammatory states. interferon JAK-STAT signaling pathway signal transduction gene regulation ISGF3 GAF Immunologic diseases. Allergy Kensei Kishimoto verfasserin aut Catera L. Wilder verfasserin aut Justin Buchanan verfasserin aut Minh Nguyen verfasserin aut Minh Nguyen verfasserin aut Chidera Okeke verfasserin aut Chidera Okeke verfasserin aut Alexander Hoffmann verfasserin aut Alexander Hoffmann verfasserin aut Quen J. Cheng verfasserin aut Quen J. Cheng verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 12(2021) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:12 year:2021 https://doi.org/10.3389/fimmu.2021.651254 kostenfrei https://doaj.org/article/4989123231dd488dbb9bb4729c3cfccf kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2021.651254/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2021 |
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10.3389/fimmu.2021.651254 doi (DE-627)DOAJ06890746X (DE-599)DOAJ4989123231dd488dbb9bb4729c3cfccf DE-627 ger DE-627 rakwb eng RC581-607 Kensei Kishimoto verfasserin aut High Dose IFN-β Activates GAF to Enhance Expression of ISGF3 Target Genes in MLE12 Epithelial Cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Interferon β (IFN-β) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN-β activates a second transcription factor complex, γ-activated factor (GAF), but the significance of this coordinated activation is unclear. We report that in murine lung epithelial cells (MLE12) high doses of IFN-β indeed activate both ISGF3 and GAF, which bind to distinct genomic locations defined by their respective DNA sequence motifs. In contrast, low doses of IFN-β preferentially activate ISGF3 but not GAF. Surprisingly, in MLE12 cells GAF binding does not induce nearby gene expression even when strongly bound to the promoter. Yet expression of interferon stimulated genes is enhanced when GAF and ISGF3 are both active compared to ISGF3 alone. We propose that GAF may function as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity and establish pro-inflammatory states. interferon JAK-STAT signaling pathway signal transduction gene regulation ISGF3 GAF Immunologic diseases. Allergy Kensei Kishimoto verfasserin aut Catera L. Wilder verfasserin aut Justin Buchanan verfasserin aut Minh Nguyen verfasserin aut Minh Nguyen verfasserin aut Chidera Okeke verfasserin aut Chidera Okeke verfasserin aut Alexander Hoffmann verfasserin aut Alexander Hoffmann verfasserin aut Quen J. Cheng verfasserin aut Quen J. Cheng verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 12(2021) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:12 year:2021 https://doi.org/10.3389/fimmu.2021.651254 kostenfrei https://doaj.org/article/4989123231dd488dbb9bb4729c3cfccf kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2021.651254/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2021 |
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10.3389/fimmu.2021.651254 doi (DE-627)DOAJ06890746X (DE-599)DOAJ4989123231dd488dbb9bb4729c3cfccf DE-627 ger DE-627 rakwb eng RC581-607 Kensei Kishimoto verfasserin aut High Dose IFN-β Activates GAF to Enhance Expression of ISGF3 Target Genes in MLE12 Epithelial Cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Interferon β (IFN-β) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN-β activates a second transcription factor complex, γ-activated factor (GAF), but the significance of this coordinated activation is unclear. We report that in murine lung epithelial cells (MLE12) high doses of IFN-β indeed activate both ISGF3 and GAF, which bind to distinct genomic locations defined by their respective DNA sequence motifs. In contrast, low doses of IFN-β preferentially activate ISGF3 but not GAF. Surprisingly, in MLE12 cells GAF binding does not induce nearby gene expression even when strongly bound to the promoter. Yet expression of interferon stimulated genes is enhanced when GAF and ISGF3 are both active compared to ISGF3 alone. We propose that GAF may function as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity and establish pro-inflammatory states. interferon JAK-STAT signaling pathway signal transduction gene regulation ISGF3 GAF Immunologic diseases. Allergy Kensei Kishimoto verfasserin aut Catera L. Wilder verfasserin aut Justin Buchanan verfasserin aut Minh Nguyen verfasserin aut Minh Nguyen verfasserin aut Chidera Okeke verfasserin aut Chidera Okeke verfasserin aut Alexander Hoffmann verfasserin aut Alexander Hoffmann verfasserin aut Quen J. Cheng verfasserin aut Quen J. Cheng verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 12(2021) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:12 year:2021 https://doi.org/10.3389/fimmu.2021.651254 kostenfrei https://doaj.org/article/4989123231dd488dbb9bb4729c3cfccf kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2021.651254/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2021 |
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10.3389/fimmu.2021.651254 doi (DE-627)DOAJ06890746X (DE-599)DOAJ4989123231dd488dbb9bb4729c3cfccf DE-627 ger DE-627 rakwb eng RC581-607 Kensei Kishimoto verfasserin aut High Dose IFN-β Activates GAF to Enhance Expression of ISGF3 Target Genes in MLE12 Epithelial Cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Interferon β (IFN-β) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN-β activates a second transcription factor complex, γ-activated factor (GAF), but the significance of this coordinated activation is unclear. We report that in murine lung epithelial cells (MLE12) high doses of IFN-β indeed activate both ISGF3 and GAF, which bind to distinct genomic locations defined by their respective DNA sequence motifs. In contrast, low doses of IFN-β preferentially activate ISGF3 but not GAF. Surprisingly, in MLE12 cells GAF binding does not induce nearby gene expression even when strongly bound to the promoter. Yet expression of interferon stimulated genes is enhanced when GAF and ISGF3 are both active compared to ISGF3 alone. We propose that GAF may function as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity and establish pro-inflammatory states. interferon JAK-STAT signaling pathway signal transduction gene regulation ISGF3 GAF Immunologic diseases. Allergy Kensei Kishimoto verfasserin aut Catera L. Wilder verfasserin aut Justin Buchanan verfasserin aut Minh Nguyen verfasserin aut Minh Nguyen verfasserin aut Chidera Okeke verfasserin aut Chidera Okeke verfasserin aut Alexander Hoffmann verfasserin aut Alexander Hoffmann verfasserin aut Quen J. Cheng verfasserin aut Quen J. Cheng verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 12(2021) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:12 year:2021 https://doi.org/10.3389/fimmu.2021.651254 kostenfrei https://doaj.org/article/4989123231dd488dbb9bb4729c3cfccf kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2021.651254/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2021 |
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10.3389/fimmu.2021.651254 doi (DE-627)DOAJ06890746X (DE-599)DOAJ4989123231dd488dbb9bb4729c3cfccf DE-627 ger DE-627 rakwb eng RC581-607 Kensei Kishimoto verfasserin aut High Dose IFN-β Activates GAF to Enhance Expression of ISGF3 Target Genes in MLE12 Epithelial Cells 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Interferon β (IFN-β) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN-β activates a second transcription factor complex, γ-activated factor (GAF), but the significance of this coordinated activation is unclear. We report that in murine lung epithelial cells (MLE12) high doses of IFN-β indeed activate both ISGF3 and GAF, which bind to distinct genomic locations defined by their respective DNA sequence motifs. In contrast, low doses of IFN-β preferentially activate ISGF3 but not GAF. Surprisingly, in MLE12 cells GAF binding does not induce nearby gene expression even when strongly bound to the promoter. Yet expression of interferon stimulated genes is enhanced when GAF and ISGF3 are both active compared to ISGF3 alone. We propose that GAF may function as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity and establish pro-inflammatory states. interferon JAK-STAT signaling pathway signal transduction gene regulation ISGF3 GAF Immunologic diseases. Allergy Kensei Kishimoto verfasserin aut Catera L. Wilder verfasserin aut Justin Buchanan verfasserin aut Minh Nguyen verfasserin aut Minh Nguyen verfasserin aut Chidera Okeke verfasserin aut Chidera Okeke verfasserin aut Alexander Hoffmann verfasserin aut Alexander Hoffmann verfasserin aut Quen J. Cheng verfasserin aut Quen J. Cheng verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 12(2021) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:12 year:2021 https://doi.org/10.3389/fimmu.2021.651254 kostenfrei https://doaj.org/article/4989123231dd488dbb9bb4729c3cfccf kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2021.651254/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2021 |
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High Dose IFN-β Activates GAF to Enhance Expression of ISGF3 Target Genes in MLE12 Epithelial Cells |
abstract |
Interferon β (IFN-β) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN-β activates a second transcription factor complex, γ-activated factor (GAF), but the significance of this coordinated activation is unclear. We report that in murine lung epithelial cells (MLE12) high doses of IFN-β indeed activate both ISGF3 and GAF, which bind to distinct genomic locations defined by their respective DNA sequence motifs. In contrast, low doses of IFN-β preferentially activate ISGF3 but not GAF. Surprisingly, in MLE12 cells GAF binding does not induce nearby gene expression even when strongly bound to the promoter. Yet expression of interferon stimulated genes is enhanced when GAF and ISGF3 are both active compared to ISGF3 alone. We propose that GAF may function as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity and establish pro-inflammatory states. |
abstractGer |
Interferon β (IFN-β) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN-β activates a second transcription factor complex, γ-activated factor (GAF), but the significance of this coordinated activation is unclear. We report that in murine lung epithelial cells (MLE12) high doses of IFN-β indeed activate both ISGF3 and GAF, which bind to distinct genomic locations defined by their respective DNA sequence motifs. In contrast, low doses of IFN-β preferentially activate ISGF3 but not GAF. Surprisingly, in MLE12 cells GAF binding does not induce nearby gene expression even when strongly bound to the promoter. Yet expression of interferon stimulated genes is enhanced when GAF and ISGF3 are both active compared to ISGF3 alone. We propose that GAF may function as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity and establish pro-inflammatory states. |
abstract_unstemmed |
Interferon β (IFN-β) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN-β activates a second transcription factor complex, γ-activated factor (GAF), but the significance of this coordinated activation is unclear. We report that in murine lung epithelial cells (MLE12) high doses of IFN-β indeed activate both ISGF3 and GAF, which bind to distinct genomic locations defined by their respective DNA sequence motifs. In contrast, low doses of IFN-β preferentially activate ISGF3 but not GAF. Surprisingly, in MLE12 cells GAF binding does not induce nearby gene expression even when strongly bound to the promoter. Yet expression of interferon stimulated genes is enhanced when GAF and ISGF3 are both active compared to ISGF3 alone. We propose that GAF may function as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity and establish pro-inflammatory states. |
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title_short |
High Dose IFN-β Activates GAF to Enhance Expression of ISGF3 Target Genes in MLE12 Epithelial Cells |
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