Exploring histone loading on HIV DNA reveals a dynamic nucleosome positioning between unintegrated and integrated viral genome
| Autor: | David Depierre, Gaël Petitjean, Heng-Chang Chen, Olivier Cuvier, Monsef Benkirane, Cécile Doyen, Motoki Takaku, Shinichi Machida, Suzie Thenin-Houssier |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Gene Expression Regulation
Viral Transcription Genetic Virus Integration HIV Infections histone Genome Viral Biology Microbiology Histones 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Transcription (biology) Humans Nucleosome 030304 developmental biology 0303 health sciences Multidisciplinary Terminal Repeat Sequences virus diseases HIV Biological Sciences Chromatin Assembly and Disassembly Long terminal repeat Nucleosomes 3. Good health Chromatin Cell biology Histone chemistry unintegrated viral DNA DNA Viral HIV-1 biology.protein H3K4me3 transcription Hypersensitive site nucleosome positioning 030217 neurology & neurosurgery DNA |
| Zdroj: | Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 0027-8424 |
| DOI: | 10.1073/pnas.1913754117 |
| Popis: | Significance The biology of HIV DNA, from its synthesis to its integration into the host genome, remains poorly understood. Here we show that in the nucleus, histones are rapidly loaded on newly synthesized unintegrated HIV DNA. Interestingly, the chromatin architecture around the HIV long terminal repeat (LTR) is different in unintegrated and integrated HIV DNA. Specifically, a nucleosome present only on the DNase hypersensitive site of unintegrated HIV DNA contributes to the transcriptional silencing of unintegrated HIV DNA by preventing RNAPII recruitment. The aim of the present study was to understand the biology of unintegrated HIV-1 DNA and reveal the mechanisms involved in its transcriptional silencing. We found that histones are loaded on HIV-1 DNA after its nuclear import and before its integration in the host genome. Nucleosome positioning analysis along the unintegrated and integrated viral genomes revealed major differences in nucleosome density and position. Indeed, in addition to the well-known nucleosomes Nuc0, Nuc1, and Nuc2 loaded on integrated HIV-1 DNA, we also found NucDHS, a nucleosome that covers the DNase hypersensitive site, in unintegrated viral DNA. In addition, unintegrated viral DNA-associated Nuc0 and Nuc2 were positioned slightly more to the 5′ end relative to their position in integrated DNA. The presence of NucDHS in the proximal region of the long terminal repeat (LTR) promoter was associated with the absence of RNAPII and of the active histone marks H3K4me3 and H3ac at the LTR. Conversely, analysis of integrated HIV-1 DNA showed a loss of NucDHS, loading of RNAPII, and enrichment in active histone marks within the LTR. We propose that unintegrated HIV-1 DNA adopts a repressive chromatin structure that competes with the transcription machinery, leading to its silencing. |
| Databáze: | OpenAIRE |
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