The Transcriptional Repressor Polycomb Group Factor 6, PCGF6, Negatively Regulates Dendritic Cell Activation and Promotes Quiescence
Pro-inflammatory signals provided by the microenvironment are critical to activate dendritic cells (DCs), components of the innate immune system that shape both innate and adaptive immunity. However, to prevent inappropriate immune activation, mechanisms must be in place to restrain DC activation to...
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Elsevier
2016-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716309445 |
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doaj-8c33a8fcc6be440dae00c85bc3811e392020-11-25T01:33:19ZengElsevierCell Reports2211-12472016-08-011671829183710.1016/j.celrep.2016.07.026The Transcriptional Repressor Polycomb Group Factor 6, PCGF6, Negatively Regulates Dendritic Cell Activation and Promotes QuiescenceGiselle M. Boukhaled0Brendan Cordeiro1Genevieve Deblois2Vassil Dimitrov3Swneke D. Bailey4Thomas Holowka5Anisa Domi6Hannah Guak7Huai-Hsuan Clare Chiu8Bart Everts9Edward J. Pearce10Mathieu Lupien11John H. White12Connie M. Krawczyk13Goodman Cancer Research Center, Departments of Microbiology and Immunology and Physiology, McGill University, Montreal, QC H3G 1Y6, CanadaGoodman Cancer Research Center, Departments of Microbiology and Immunology and Physiology, McGill University, Montreal, QC H3G 1Y6, CanadaThe Princess Margaret Cancer Centre, University Health Network, Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, CanadaDepartment of Physiology, McGill University, Montreal, QC H3G 1Y6, CanadaThe Princess Margaret Cancer Centre, University Health Network, Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, CanadaDepartment of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Faculty of Biology, University of Freiburg, Freiburg, Freiburg 79104, GermanyGoodman Cancer Research Center, Departments of Microbiology and Immunology and Physiology, McGill University, Montreal, QC H3G 1Y6, CanadaGoodman Cancer Research Center, Departments of Microbiology and Immunology and Physiology, McGill University, Montreal, QC H3G 1Y6, CanadaGoodman Cancer Research Center, Departments of Microbiology and Immunology and Physiology, McGill University, Montreal, QC H3G 1Y6, CanadaDepartment of Parasitology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, the NetherlandsDepartment of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Faculty of Biology, University of Freiburg, Freiburg, Freiburg 79104, GermanyThe Princess Margaret Cancer Centre, University Health Network, Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, CanadaDepartment of Physiology, McGill University, Montreal, QC H3G 1Y6, CanadaGoodman Cancer Research Center, Departments of Microbiology and Immunology and Physiology, McGill University, Montreal, QC H3G 1Y6, CanadaPro-inflammatory signals provided by the microenvironment are critical to activate dendritic cells (DCs), components of the innate immune system that shape both innate and adaptive immunity. However, to prevent inappropriate immune activation, mechanisms must be in place to restrain DC activation to ensure DCs are activated only once sufficient stimuli have been received. Here, we report that DC activation and immunogenicity are regulated by the transcriptional repressor Polycomb group factor 6 (PCGF6). Pcgf6 is rapidly downregulated upon stimulation, and this downregulation is necessary to permit full DC activation. Silencing PCGF6 expression enhanced both spontaneous and stimulated DC activation. We show that PCGF6 associates with the H3K4me3 demethylase JARID1c, and together, they negatively regulate H3K4me3 levels in DCs. Our results identify two key regulators, PCGF6 and JARID1c that temper DC activation and implicate active transcriptional silencing via histone demethylation as a previously unappreciated mechanism for regulating DC activation and quiescence.http://www.sciencedirect.com/science/article/pii/S2211124716309445 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Giselle M. Boukhaled Brendan Cordeiro Genevieve Deblois Vassil Dimitrov Swneke D. Bailey Thomas Holowka Anisa Domi Hannah Guak Huai-Hsuan Clare Chiu Bart Everts Edward J. Pearce Mathieu Lupien John H. White Connie M. Krawczyk |
| spellingShingle |
Giselle M. Boukhaled Brendan Cordeiro Genevieve Deblois Vassil Dimitrov Swneke D. Bailey Thomas Holowka Anisa Domi Hannah Guak Huai-Hsuan Clare Chiu Bart Everts Edward J. Pearce Mathieu Lupien John H. White Connie M. Krawczyk The Transcriptional Repressor Polycomb Group Factor 6, PCGF6, Negatively Regulates Dendritic Cell Activation and Promotes Quiescence Cell Reports |
| author_facet |
Giselle M. Boukhaled Brendan Cordeiro Genevieve Deblois Vassil Dimitrov Swneke D. Bailey Thomas Holowka Anisa Domi Hannah Guak Huai-Hsuan Clare Chiu Bart Everts Edward J. Pearce Mathieu Lupien John H. White Connie M. Krawczyk |
| author_sort |
Giselle M. Boukhaled |
| title |
The Transcriptional Repressor Polycomb Group Factor 6, PCGF6, Negatively Regulates Dendritic Cell Activation and Promotes Quiescence |
| title_short |
The Transcriptional Repressor Polycomb Group Factor 6, PCGF6, Negatively Regulates Dendritic Cell Activation and Promotes Quiescence |
| title_full |
The Transcriptional Repressor Polycomb Group Factor 6, PCGF6, Negatively Regulates Dendritic Cell Activation and Promotes Quiescence |
| title_fullStr |
The Transcriptional Repressor Polycomb Group Factor 6, PCGF6, Negatively Regulates Dendritic Cell Activation and Promotes Quiescence |
| title_full_unstemmed |
The Transcriptional Repressor Polycomb Group Factor 6, PCGF6, Negatively Regulates Dendritic Cell Activation and Promotes Quiescence |
| title_sort |
transcriptional repressor polycomb group factor 6, pcgf6, negatively regulates dendritic cell activation and promotes quiescence |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2016-08-01 |
| description |
Pro-inflammatory signals provided by the microenvironment are critical to activate dendritic cells (DCs), components of the innate immune system that shape both innate and adaptive immunity. However, to prevent inappropriate immune activation, mechanisms must be in place to restrain DC activation to ensure DCs are activated only once sufficient stimuli have been received. Here, we report that DC activation and immunogenicity are regulated by the transcriptional repressor Polycomb group factor 6 (PCGF6). Pcgf6 is rapidly downregulated upon stimulation, and this downregulation is necessary to permit full DC activation. Silencing PCGF6 expression enhanced both spontaneous and stimulated DC activation. We show that PCGF6 associates with the H3K4me3 demethylase JARID1c, and together, they negatively regulate H3K4me3 levels in DCs. Our results identify two key regulators, PCGF6 and JARID1c that temper DC activation and implicate active transcriptional silencing via histone demethylation as a previously unappreciated mechanism for regulating DC activation and quiescence. |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124716309445 |
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