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Exploring histone loading on HIV DNA reveals a dynamic nucleosome positioning between unintegrated and integrated viral genome
- Source :
- Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences of the United States of America
- Publication Year :
- 2020
-
Abstract
- 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.<br />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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 00278424
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....a3e30a706757777a03166bb5becfc8a2
- Full Text :
- https://doi.org/10.1073/pnas.1913754117