IFI16, a nuclear innate immune DNA sensor, mediates epigenetic silencing of herpesvirus genomes by its association with H3K9 methyltransferases SUV39H1 and GLP
IFI16, an innate immune DNA sensor, recognizes the nuclear episomal herpes viral genomes and induces the inflammasome and interferon-β responses. IFI16 also regulates cellular transcription and act as a DNA virus restriction factor. IFI16 knockdown disrupted the latency of Kaposi’s sarcoma associate...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2019-11-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/49500 |
| _version_ | 1811199573003075584 |
|---|---|
| author | Arunava Roy Anandita Ghosh Binod Kumar Bala Chandran |
| author_facet | Arunava Roy Anandita Ghosh Binod Kumar Bala Chandran |
| author_sort | Arunava Roy |
| collection | DOAJ |
| description | IFI16, an innate immune DNA sensor, recognizes the nuclear episomal herpes viral genomes and induces the inflammasome and interferon-β responses. IFI16 also regulates cellular transcription and act as a DNA virus restriction factor. IFI16 knockdown disrupted the latency of Kaposi’s sarcoma associated herpesvirus (KSHV) and induced lytic transcripts. However, the mechanism of IFI16’s transcription regulation is unknown. Here, we show that IFI16 is in complex with the H3K9 methyltransferase SUV39H1 and GLP and recruits them to the KSHV genome during de novo infection and latency. The resulting depositions of H3K9me2/me3 serve as a docking site for the heterochromatin-inducing HP1α protein leading into the IFI16-dependent epigenetic modifications and silencing of KSHV lytic genes. These studies suggest that IFI16’s interaction with H3K9MTases is one of the potential mechanisms by which IFI16 regulates transcription and establish an important paradigm of an innate immune sensor’s involvement in epigenetic silencing of foreign DNA. |
| first_indexed | 2024-04-12T01:49:51Z |
| format | Article |
| id | doaj.art-d2b22504b8624dccbc098da947c3e0c6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:49:51Z |
| publishDate | 2019-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-d2b22504b8624dccbc098da947c3e0c62022-12-22T03:52:58ZengeLife Sciences Publications LtdeLife2050-084X2019-11-01810.7554/eLife.49500IFI16, a nuclear innate immune DNA sensor, mediates epigenetic silencing of herpesvirus genomes by its association with H3K9 methyltransferases SUV39H1 and GLPArunava Roy0https://orcid.org/0000-0002-8486-0539Anandita Ghosh1Binod Kumar2Bala Chandran3https://orcid.org/0000-0002-5319-8714Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, United StatesDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, United StatesDepartment of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, United StatesDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, United StatesIFI16, an innate immune DNA sensor, recognizes the nuclear episomal herpes viral genomes and induces the inflammasome and interferon-β responses. IFI16 also regulates cellular transcription and act as a DNA virus restriction factor. IFI16 knockdown disrupted the latency of Kaposi’s sarcoma associated herpesvirus (KSHV) and induced lytic transcripts. However, the mechanism of IFI16’s transcription regulation is unknown. Here, we show that IFI16 is in complex with the H3K9 methyltransferase SUV39H1 and GLP and recruits them to the KSHV genome during de novo infection and latency. The resulting depositions of H3K9me2/me3 serve as a docking site for the heterochromatin-inducing HP1α protein leading into the IFI16-dependent epigenetic modifications and silencing of KSHV lytic genes. These studies suggest that IFI16’s interaction with H3K9MTases is one of the potential mechanisms by which IFI16 regulates transcription and establish an important paradigm of an innate immune sensor’s involvement in epigenetic silencing of foreign DNA.https://elifesciences.org/articles/49500KSHV epigeneticsIFI16 and KSHV gene silencingKSHV latencyinnate sensinghost methyltransferasesepigenetic silencing |
| spellingShingle | Arunava Roy Anandita Ghosh Binod Kumar Bala Chandran IFI16, a nuclear innate immune DNA sensor, mediates epigenetic silencing of herpesvirus genomes by its association with H3K9 methyltransferases SUV39H1 and GLP eLife KSHV epigenetics IFI16 and KSHV gene silencing KSHV latency innate sensing host methyltransferases epigenetic silencing |
| title | IFI16, a nuclear innate immune DNA sensor, mediates epigenetic silencing of herpesvirus genomes by its association with H3K9 methyltransferases SUV39H1 and GLP |
| title_full | IFI16, a nuclear innate immune DNA sensor, mediates epigenetic silencing of herpesvirus genomes by its association with H3K9 methyltransferases SUV39H1 and GLP |
| title_fullStr | IFI16, a nuclear innate immune DNA sensor, mediates epigenetic silencing of herpesvirus genomes by its association with H3K9 methyltransferases SUV39H1 and GLP |
| title_full_unstemmed | IFI16, a nuclear innate immune DNA sensor, mediates epigenetic silencing of herpesvirus genomes by its association with H3K9 methyltransferases SUV39H1 and GLP |
| title_short | IFI16, a nuclear innate immune DNA sensor, mediates epigenetic silencing of herpesvirus genomes by its association with H3K9 methyltransferases SUV39H1 and GLP |
| title_sort | ifi16 a nuclear innate immune dna sensor mediates epigenetic silencing of herpesvirus genomes by its association with h3k9 methyltransferases suv39h1 and glp |
| topic | KSHV epigenetics IFI16 and KSHV gene silencing KSHV latency innate sensing host methyltransferases epigenetic silencing |
| url | https://elifesciences.org/articles/49500 |
| work_keys_str_mv | AT arunavaroy ifi16anuclearinnateimmunednasensormediatesepigeneticsilencingofherpesvirusgenomesbyitsassociationwithh3k9methyltransferasessuv39h1andglp AT ananditaghosh ifi16anuclearinnateimmunednasensormediatesepigeneticsilencingofherpesvirusgenomesbyitsassociationwithh3k9methyltransferasessuv39h1andglp AT binodkumar ifi16anuclearinnateimmunednasensormediatesepigeneticsilencingofherpesvirusgenomesbyitsassociationwithh3k9methyltransferasessuv39h1andglp AT balachandran ifi16anuclearinnateimmunednasensormediatesepigeneticsilencingofherpesvirusgenomesbyitsassociationwithh3k9methyltransferasessuv39h1andglp |