CAF-1 promotes HIV-1 latency by leading the formation of phase-separated suppressive nuclear bodies.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA700535 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13649912_1.fastq.gz | Fastqsanger.gz | |||
| SRR13649912_2.fastq.gz | Fastqsanger.gz | |||
| SRR13649913_1.fastq.gz | Fastqsanger.gz | |||
| SRR13649913_2.fastq.gz | Fastqsanger.gz | |||
| SRR13649914_1.fastq.gz | Fastqsanger.gz |
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Project description:HIV-1 latency is a major obstacle to achieve a functional cure for AIDS. To eradicate the viral reservoir, one of the strategies is to specifically reactivate HIV-1-infected cells and followed by elimination with potent immune surveillance. However, present latency-reversing agents (LRAs) are quite dissatisfactory because of their high toxicity and low efficiency. New targets need to be identified to develop more promising LRAs. Here, we found that histone chaperone chromatin assembly factor 1 (CAF-1) promotes HIV-1 latency by forming versatile suppressive nuclear bodies. CAF-1 plays a leading role for the formation of bodies recruiting multi-layer suppressive epigenetic modifiers and maintainers, and is of the characteristic of liquid-liquid phase separation (LLPS). Three distinct disordered regions of CHAF1A subunit coalesce CAF-1 body components by forming LLPS and play a key in maintaining HIV-1 latency. Therefore, disruptive induction of phase-separated CAF-1 body could be an important strategy to reactivate latent HIV-1.
2021-02-09 | GSE166337 | GEO
Project description:HIV-1 latency is a major obstacle to achieve a functional cure for AIDS. To eradicate the viral reservoir, one of the strategies is to specifically reactivate HIV-1-infected cells and followed by elimination with potent immune surveillance. However, present latency-reversing agents (LRAs) are quite dissatisfactory because of their high toxicity and low efficiency. New targets need to be identified to develop more promising LRAs. Here, we found that histone chaperone chromatin assembly factor 1 (CAF-1) promotes HIV-1 latency by forming versatile suppressive nuclear bodies. CAF-1 plays a leading role for the formation of bodies recruiting multi-layer suppressive epigenetic modifiers and maintainers, and is of the characteristic of liquid-liquid phase separation (LLPS). Three distinct disordered regions of CHAF1A subunit coalesce CAF-1 body components by forming LLPS and play a key in maintaining HIV-1 latency. Therefore, disruptive induction of phase-separated CAF-1 body could be an important strategy to reactivate latent HIV-1.
2021-02-09 | PXD024172 |
Project description:HIV-1 latency is a major obstacle to achieving a functional cure for AIDS. Reactivation of HIV-1-infected cells followed by their elimination via immune surveillance is one proposed strategy for eradicating the viral reservoir. However, current latency-reversing agents (LRAs) show high toxicity and low efficiency, and new targets are needed to develop more promising LRAs. Here, we found that the histone chaperone CAF-1 (chromatin assembly factor 1) is enriched on the HIV-1 long terminal repeat (LTR) and forms nuclear bodies with liquid-liquid phase separation (LLPS) properties. CAF-1 recruits epigenetic modifiers and histone chaperones to the nuclear bodies to establish and maintain HIV-1 latency in different latency models and primary CD4+ T cells. Three disordered regions of the CHAF1A subunit are important for phase-separated CAF-1 nuclear body formation and play a key role in maintaining HIV-1 latency. Disruption of phase-separated CAF-1 bodies could be a potential strategy to reactivate latent HIV-1.
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Project description:Molecular mechanisms of HIV-1 latency have been studied extensively to achieve a functional cure for the acquired immunodeficiency syndrome (AIDS). To develop more promising latency-reversing agents (LRAs) to efficiently reactivate the latent reservoir which is subsequently eliminated by immune surveillance, new therapeutic targets need to be evaluated. Here, we found that the Polycomb group (PcG) protein CBX4 contributes to HIV-1 latency in many latency models and primary CD4+ T cells. CBX4 forms nuclear bodies with liquid–liquid phase separation (LLPS) properties on the HIV-1 long terminal repeat (LTR). Further proteomics analysis revealed that CBX4 recruits EZH2 to CBX4 bodies and SUMOylates EZH2 utilizing its SUMO E3 ligase activity, which enhances the H3K27 methyltransferase activity of EZH2. Our results indicated that CBX4 bridges the Polycomb repressive complex 1 (PRC1) and PRC2, resulting in synergistically maintaining HIV-1 latency. Dissolution of phase-separated CBX4 bodies could be a potential intervention to reactivate latent HIV-1.
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Project description:During every cell cycle, both the genome and the associated chromatin must be accurately replicated. Chromatin Assembly Factor-1 (CAF-1) is a key regulator of chromatin replication, but how CAF-1 functions in relation to the DNA replication machinery is unknown. Here, we reveal that this crosstalk differs between the leading and lagging strand at replication forks. Using biochemical reconstitution, we show that DNA and histones promote CAF-1 recruitment to its binding partner PCNA and reveal that two CAF-1 complexes are required for efficient nucleosome assembly under these conditions. Remarkably, in the context of the replisome, CAF-1 competes with the leading strand DNA polymerase epsilon (Pole) for PCNA binding. However, CAF-1 does not affect the activity of the lagging strand DNA polymerase Delta (Pold). Yet, in cells, CAF-1 deposits newly synthesized histones equally on both daughter strands. Thus, on the leading strand, chromatin assembly by CAF-1 cannot occur simultaneously to DNA synthesis, while on the lagging strand these processes may be coupled. We propose that these differences may facilitate distinct parental histone recycling mechanisms and accommodate the inherent asymmetry of DNA replication.
2023-08-08 | GSE223782 | GEO
Project description:Compare the difference between pairwise aNOF and CAF samples for two patients patient #225: aNOF #225 vs CAF #225 patient #248: aNOF #248 vs CAF #248
2012-01-27 | E-GEOD-35249 | biostudies-arrayexpress
Project description:Gene expression profiling of CAF co-cultured with human oral squamous cell carcinoma (OSCC) cells compared with mono-cultured CAF. To identify key molecular regulators expressed by carcinoma-associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing co-cultured OSCC cells and CAF with monoculture controls. comparison 1: CAF co-cultured with OSCC vs. mono-cultured CAF comparison 2: OSCC co-cultured with CAF vs. mono-cultured OSCC 1.7X10(5) YD-10B OSCC cells and 1.7X10(5) CAF were seeded in the upper chamber and lower chamber, respectively, of 6-transwell plates containing collagen-coated 1 micrometer pore transmembrane filters (Becton Dickinson, Franklin Lakes, NJ, USA). Monoculture control samples were generated by culturing only CAF or OSCC on the same side of the filter as in the co-culture design.
2010-06-21 | E-GEOD-18532 | biostudies-arrayexpress
Project description:The retrovirus HIV-1 integrates into the host genome and establishes a latent viral reservoir that escapes immune surveillance. Molecular mechanisms of HIV-1 latency have been studied extensively to achieve a cure for the acquired immunodeficiency syndrome (AIDS). Latency-reversing agents (LRAs) have been developed to reactivate and eliminate the latent reservoir by the immune system. To develop more promising LRAs, it is essential to evaluate new therapeutic targets. Here, we find that CBX4, a component of the Polycomb Repressive Complex 1 (PRC1), contributes to HIV-1 latency in seven latency models and primary CD4+ T cells. CBX4 forms nuclear bodies with liquid-liquid phase separation (LLPS) properties on the HIV-1 long terminal repeat (LTR) and recruits EZH2, the catalytic subunit of PRC2. CBX4 SUMOylates EZH2 utilizing its SUMO E3 ligase activity, thereby enhancing the H3K27 methyltransferase activity of EZH2. Our results indicate that CBX4 acts as a bridge between the repressor complexes PRC1 and PRC2 that act synergistically to maintain HIV-1 latency. Dissolution of phase-separated CBX4 bodies could be a potential intervention to reactivate latent HIV-1.
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Project description:Chromatin assembly factor CAF-1 is conserved in all eukaryotes. In contrast to animals, plant CAF-1 is viable. Here we probe effects of loss of CAF-1 on the transcriptome of non-diving cells. Fully expanded rosette leaf 6 was collected from 10 35-d-old plants grown in short day photoperiods of wild type Col and CAF-1 mutants fas2-4 were used for RNA extraction.
2015-11-02 | E-MTAB-2376 | biostudies-arrayexpress