Comprehensive synergy mapping links a BAF- and NSL-containing “supercomplex” to the transcriptional silencing of HIV-1
Summary: Host repressors mediate HIV latency, but how they interactively silence the virus remains unclear. Here, we develop “reiterative enrichment and authentication of CRISPRi targets for synergies (REACTS)” to probe the genome for synergies between HIV transcription repressors. Using eight known...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723010665 |
| _version_ | 1797690194498945024 |
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| author | Zichong Li Steven G. Deeks Melanie Ott Warner C. Greene |
| author_facet | Zichong Li Steven G. Deeks Melanie Ott Warner C. Greene |
| author_sort | Zichong Li |
| collection | DOAJ |
| description | Summary: Host repressors mediate HIV latency, but how they interactively silence the virus remains unclear. Here, we develop “reiterative enrichment and authentication of CRISPRi targets for synergies (REACTS)” to probe the genome for synergies between HIV transcription repressors. Using eight known host repressors as queries, we identify 32 synergies involving eleven repressors, including BCL7C, KANSL2, and SIRT2. Overexpression of these three proteins reduces HIV reactivation in Jurkat T cells and in CD4 T cells from people living with HIV on antiretroviral therapy (ART). We show that the BCL7C-containing BAF complex and the KANSL2-containing NSL complex form a “supercomplex” that increases inhibitory histone acetylation of the HIV long-terminal repeat (LTR) and its occupancy by the short variant of the acetyl-lysine reader Brd4. Collectively, we provide a validated platform for defining gene synergies genome wide, and the BAF-NSL “supercomplex” represents a potential target for overcoming HIV rebound after ART cessation. |
| first_indexed | 2024-03-12T01:56:03Z |
| format | Article |
| id | doaj.art-4eb70c48fb6e4b0bb87478023011519a |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T01:56:03Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4eb70c48fb6e4b0bb87478023011519a2023-09-08T04:33:13ZengElsevierCell Reports2211-12472023-09-01429113055Comprehensive synergy mapping links a BAF- and NSL-containing “supercomplex” to the transcriptional silencing of HIV-1Zichong Li0Steven G. Deeks1Melanie Ott2Warner C. Greene3Gladstone Institute of Virology, San Francisco, CA 94158, USA; Corresponding authorUniversity of California, San Francisco, San Francisco, CA 94143, USAGladstone Institute of Virology, San Francisco, CA 94158, USA; University of California, San Francisco, San Francisco, CA 94143, USAGladstone Institute of Virology, San Francisco, CA 94158, USA; University of California, San Francisco, San Francisco, CA 94143, USA; Corresponding authorSummary: Host repressors mediate HIV latency, but how they interactively silence the virus remains unclear. Here, we develop “reiterative enrichment and authentication of CRISPRi targets for synergies (REACTS)” to probe the genome for synergies between HIV transcription repressors. Using eight known host repressors as queries, we identify 32 synergies involving eleven repressors, including BCL7C, KANSL2, and SIRT2. Overexpression of these three proteins reduces HIV reactivation in Jurkat T cells and in CD4 T cells from people living with HIV on antiretroviral therapy (ART). We show that the BCL7C-containing BAF complex and the KANSL2-containing NSL complex form a “supercomplex” that increases inhibitory histone acetylation of the HIV long-terminal repeat (LTR) and its occupancy by the short variant of the acetyl-lysine reader Brd4. Collectively, we provide a validated platform for defining gene synergies genome wide, and the BAF-NSL “supercomplex” represents a potential target for overcoming HIV rebound after ART cessation.http://www.sciencedirect.com/science/article/pii/S2211124723010665CP: ImmunologyCP: Molecular biology |
| spellingShingle | Zichong Li Steven G. Deeks Melanie Ott Warner C. Greene Comprehensive synergy mapping links a BAF- and NSL-containing “supercomplex” to the transcriptional silencing of HIV-1 Cell Reports CP: Immunology CP: Molecular biology |
| title | Comprehensive synergy mapping links a BAF- and NSL-containing “supercomplex” to the transcriptional silencing of HIV-1 |
| title_full | Comprehensive synergy mapping links a BAF- and NSL-containing “supercomplex” to the transcriptional silencing of HIV-1 |
| title_fullStr | Comprehensive synergy mapping links a BAF- and NSL-containing “supercomplex” to the transcriptional silencing of HIV-1 |
| title_full_unstemmed | Comprehensive synergy mapping links a BAF- and NSL-containing “supercomplex” to the transcriptional silencing of HIV-1 |
| title_short | Comprehensive synergy mapping links a BAF- and NSL-containing “supercomplex” to the transcriptional silencing of HIV-1 |
| title_sort | comprehensive synergy mapping links a baf and nsl containing supercomplex to the transcriptional silencing of hiv 1 |
| topic | CP: Immunology CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723010665 |
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