Transcriptional mechanism of IRF8 and PU.1 governs microglial activation in neurodegenerative condition
ABSTRACT Microglial activation occurs in divergent neuropathological conditions. Such microglial event has the key involvement in the progression of CNS diseases. However, the transcriptional mechanism governing microglial activation remains poorly understood. Here, we investigate the microglial res...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Oxford University Press
2018-11-01
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| Series: | Protein & Cell |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1007/s13238-018-0599-3 |
| _version_ | 1797764701179871232 |
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| author | Nan Zhou Kaili Liu Yue Sun Ying Cao Jing Yang |
| author_facet | Nan Zhou Kaili Liu Yue Sun Ying Cao Jing Yang |
| author_sort | Nan Zhou |
| collection | DOAJ |
| description | ABSTRACT Microglial activation occurs in divergent neuropathological conditions. Such microglial event has the key involvement in the progression of CNS diseases. However, the transcriptional mechanism governing microglial activation remains poorly understood. Here, we investigate the microglial response to traumatic injury-induced neurodegeneration by the 3D fluorescence imaging technique. We show that transcription factors IRF8 and PU.1 are both indispensible for microglial activation, as their specific post-developmental deletion in microglia abolishes the process. Mechanistically, we reveal that IRF8 and PU.1 directly target the gene transcription of each other in a positive feedback to sustain their highly enhanced expression during microglial activation. Moreover, IRF8 and PU.1 dictate the microglial response by cooperatively acting through the composite IRF-ETS motifs that are specifically enriched on microglial activation-related genes. This action of cooperative transcription can be further verified biochemically by the synergetic binding of IRF8 and PU.1 proteins to the composite-motif DNA. Our study has therefore elucidated the central transcriptional mechanism of microglial activation in response to neurodegenerative condition. |
| first_indexed | 2024-03-12T19:59:31Z |
| format | Article |
| id | doaj.art-0b74c192f9504b948ebd0875bcb5f84c |
| institution | Directory Open Access Journal |
| issn | 1674-800X 1674-8018 |
| language | English |
| last_indexed | 2024-03-12T19:59:31Z |
| publishDate | 2018-11-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | Protein & Cell |
| spelling | doaj.art-0b74c192f9504b948ebd0875bcb5f84c2023-08-02T02:31:45ZengOxford University PressProtein & Cell1674-800X1674-80182018-11-011028710310.1007/s13238-018-0599-3Transcriptional mechanism of IRF8 and PU.1 governs microglial activation in neurodegenerative conditionNan Zhou0Kaili Liu1Yue Sun2Ying Cao3Jing Yang4School of Medicine, Tsinghua UniversityCenter for Life Sciences, Peking UniversityState Key Laboratory of Membrane Biology, Peking UniversityState Key Laboratory of Membrane Biology, Peking UniversityState Key Laboratory of Membrane Biology, Peking UniversityABSTRACT Microglial activation occurs in divergent neuropathological conditions. Such microglial event has the key involvement in the progression of CNS diseases. However, the transcriptional mechanism governing microglial activation remains poorly understood. Here, we investigate the microglial response to traumatic injury-induced neurodegeneration by the 3D fluorescence imaging technique. We show that transcription factors IRF8 and PU.1 are both indispensible for microglial activation, as their specific post-developmental deletion in microglia abolishes the process. Mechanistically, we reveal that IRF8 and PU.1 directly target the gene transcription of each other in a positive feedback to sustain their highly enhanced expression during microglial activation. Moreover, IRF8 and PU.1 dictate the microglial response by cooperatively acting through the composite IRF-ETS motifs that are specifically enriched on microglial activation-related genes. This action of cooperative transcription can be further verified biochemically by the synergetic binding of IRF8 and PU.1 proteins to the composite-motif DNA. Our study has therefore elucidated the central transcriptional mechanism of microglial activation in response to neurodegenerative condition.http://link.springer.com/article/10.1007/s13238-018-0599-3microglia3D fluorescence imaging techniqueneurodegenerationIRF8PU.1 |
| spellingShingle | Nan Zhou Kaili Liu Yue Sun Ying Cao Jing Yang Transcriptional mechanism of IRF8 and PU.1 governs microglial activation in neurodegenerative condition Protein & Cell microglia 3D fluorescence imaging technique neurodegeneration IRF8 PU.1 |
| title | Transcriptional mechanism of IRF8 and PU.1 governs microglial activation in neurodegenerative condition |
| title_full | Transcriptional mechanism of IRF8 and PU.1 governs microglial activation in neurodegenerative condition |
| title_fullStr | Transcriptional mechanism of IRF8 and PU.1 governs microglial activation in neurodegenerative condition |
| title_full_unstemmed | Transcriptional mechanism of IRF8 and PU.1 governs microglial activation in neurodegenerative condition |
| title_short | Transcriptional mechanism of IRF8 and PU.1 governs microglial activation in neurodegenerative condition |
| title_sort | transcriptional mechanism of irf8 and pu 1 governs microglial activation in neurodegenerative condition |
| topic | microglia 3D fluorescence imaging technique neurodegeneration IRF8 PU.1 |
| url | http://link.springer.com/article/10.1007/s13238-018-0599-3 |
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