Ontology highlight
ABSTRACT:
PROVIDER: PRJNA905178 | ENA |
REPOSITORIES: ENA
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Project description:In order to identify novel factors associated with regulation of HIV-1 transcription, we completed a genome-wide CRISPRi screen in a monogenic model of HIV-1. We identified SLTM mediated suppression of HIV-1 transcription. We hypothesized that SLTM would alter the chromatin acessibility at the site of HIV-1 integration. We conducted ATAC-seq of CRISPR ready cells encoding a single HIV-1 provirus in the SPECC1 gene transduced with a gRNA targetting SLTM and a Non-Targeting gRNA. We found that SLTM knockdown increased HIV-1 proviral acessibility across the provirus and host acessibility downstream of the site of HIV-1 integration.
2022-05-20 | GSE203235 | GEO
Project description:Impact of proteasome inhibition on nascent transcription of APOBEC3 cytidine deaminases
| PRJNA1041408 | ENA
Project description:The three-dimensional structure of the genome is a regulator of transcription and cell function; HIV-1 infection can influence host cell function, but the degree to which this is mediated through changes to host chromatin architecture is unclear. We interrogated genome-wide chromatin organization and the structure of chromatin around latently infected HIV-1 integration sites using Hi-C and ATAC-seq and combined these data with RNA transcriptional analysis of the provirus and neighboring genes in HIV-inducible cellular models. We found chromatin interaction networks around integrated HIV-1 are predominantly preserved with respect to uninfected cells, proving the lack of an obligate association between latent integration and major chromatin remodeling. Instead, we find that induction of proviral transcription may lead to local changes in chromatin accessibility downstream from the 3’ LTR, demonstrating that HIV-1 can alter local cellular chromatin structure post-integration. Using long-read Nanopore RNA-seq, we interrogated the local host and HIV-1 transcriptomes and observed that 1-5% of HIV-1 transcripts initiated at the 5’ LTR promoter extended into the flanking cellular genome, generating chimeric virus-host RNAs. Thus, integration leading to latency (and provirus activation) may not lead to obligate global chromatin rearrangements; we also observed, previously unreported, novel changes in chromatin accessibility during HIV-1 transcription.
2022-08-26 | GSE189178 | GEO
Project description:HIV-1 integration introduces ectopic transcription factor binding sites into host chromatin. We postulate that the integrated provirus serves as an ectopic enhancer that recruits additional transcriptional factors to the integration locus, increases chromatin accessibility, changes 3D chromatin interactions, and enhances both retroviral and host gene expression. We used 4 well-characterized HIV-1-infected cell line clones having unique integration sites and low to high levels of HIV-1 expression. Using single-cell DOGMA-seq, which captured the heterogeneity of HIV-1 expression and host chromatin accessibility, we found that HIV-1 transcription correlated with HIV-1 accessibility and host chromatin accessibility. HIV-1 integration increased local host chromatin accessibility within ~5–30 kb distance. CRISPRa and CRISPRi-mediated HIV-1 promoter activation and inhibition confirmed integration site-dependent HIV-1-driven changes of host chromatin accessibility. HIV-1 did not drive chromatin confirmation changes at the genomic level (by Hi-C) or the enhancer connectome (by H3K27Ac HiChIP). Using 4C-seq to interrogate HIV-1-chromatin interactions, we found that HIV-1 interacted with host chromatin ~100–300 kb from the integration site. By identifying chromatin regions having both increased transcription factor activity (by ATAC-seq) and HIV-1-chromtain interaction (by 4C-seq), we identified enrichment of ETS, RUNT, STAT, and ZNF transcription factor binding that may mediate HIV-1-host chromatin interactions. Our study found that HIV-1 promoter activity increased host chromatin accessibility, increased HIV-1-host chromatin interactions in an integration site dependent manner, within the existing chromatin boundaries without impacting broader host chromatin structure.
2023-05-01 | GSE230313 | GEO
Project description:HIV-1 integration introduces ectopic transcription factor binding sites into host chromatin. We postulate that the integrated provirus serves as an ectopic enhancer that recruits additional transcriptional factors to the integration locus, increases chromatin accessibility, changes 3D chromatin interactions, and enhances both retroviral and host gene expression. We used 4 well-characterized HIV-1-infected cell line clones having unique integration sites and low to high levels of HIV-1 expression. Using single-cell DOGMA-seq, which captured the heterogeneity of HIV-1 expression and host chromatin accessibility, we found that HIV-1 transcription correlated with HIV-1 accessibility and host chromatin accessibility. HIV-1 integration increased local host chromatin accessibility within ~5–30 kb distance. CRISPRa and CRISPRi-mediated HIV-1 promoter activation and inhibition confirmed integration site-dependent HIV-1-driven changes of host chromatin accessibility. HIV-1 did not drive chromatin confirmation changes at the genomic level (by Hi-C) or the enhancer connectome (by H3K27Ac HiChIP). Using 4C-seq to interrogate HIV-1-chromatin interactions, we found that HIV-1 interacted with host chromatin ~100–300 kb from the integration site. By identifying chromatin regions having both increased transcription factor activity (by ATAC-seq) and HIV-1-chromtain interaction (by 4C-seq), we identified enrichment of ETS, RUNT, STAT, and ZNF transcription factor binding that may mediate HIV-1-host chromatin interactions. Our study found that HIV-1 promoter activity increased host chromatin accessibility, increased HIV-1-host chromatin interactions in an integration site dependent manner, within the existing chromatin boundaries without impacting broader host chromatin structure.
2023-05-01 | GSE229928 | GEO
Project description:HIV-1 integration introduces ectopic transcription factor binding sites into host chromatin. We postulate that the integrated provirus serves as an ectopic enhancer that recruits additional transcriptional factors to the integration locus, increases chromatin accessibility, changes 3D chromatin interactions, and enhances both retroviral and host gene expression. We used 4 well-characterized HIV-1-infected cell line clones having unique integration sites and low to high levels of HIV-1 expression. Using single-cell DOGMA-seq, which captured the heterogeneity of HIV-1 expression and host chromatin accessibility, we found that HIV-1 transcription correlated with HIV-1 accessibility and host chromatin accessibility. HIV-1 integration increased local host chromatin accessibility within ~5–30 kb distance. CRISPRa and CRISPRi-mediated HIV-1 promoter activation and inhibition confirmed integration site-dependent HIV-1-driven changes of host chromatin accessibility. HIV-1 did not drive chromatin confirmation changes at the genomic level (by Hi-C) or the enhancer connectome (by H3K27Ac HiChIP). Using 4C-seq to interrogate HIV-1-chromatin interactions, we found that HIV-1 interacted with host chromatin ~100–300 kb from the integration site. By identifying chromatin regions having both increased transcription factor activity (by ATAC-seq) and HIV-1-chromtain interaction (by 4C-seq), we identified enrichment of ETS, RUNT, STAT, and ZNF transcription factor binding that may mediate HIV-1-host chromatin interactions. Our study found that HIV-1 promoter activity increased host chromatin accessibility, increased HIV-1-host chromatin interactions in an integration site dependent manner, within the existing chromatin boundaries without impacting broader host chromatin structure.
2023-05-01 | GSE229927 | GEO
Project description:HIV-1 integration introduces ectopic transcription factor binding sites into host chromatin. We postulate that the integrated provirus serves as an ectopic enhancer that recruits additional transcriptional factors to the integration locus, increases chromatin accessibility, changes 3D chromatin interactions, and enhances both retroviral and host gene expression. We used 4 well-characterized HIV-1-infected cell line clones having unique integration sites and low to high levels of HIV-1 expression. Using single-cell DOGMA-seq, which captured the heterogeneity of HIV-1 expression and host chromatin accessibility, we found that HIV-1 transcription correlated with HIV-1 accessibility and host chromatin accessibility. HIV-1 integration increased local host chromatin accessibility within ~5–30 kb distance. CRISPRa and CRISPRi-mediated HIV-1 promoter activation and inhibition confirmed integration site-dependent HIV-1-driven changes of host chromatin accessibility. HIV-1 did not drive chromatin confirmation changes at the genomic level (by Hi-C) or the enhancer connectome (by H3K27Ac HiChIP). Using 4C-seq to interrogate HIV-1-chromatin interactions, we found that HIV-1 interacted with host chromatin ~100–300 kb from the integration site. By identifying chromatin regions having both increased transcription factor activity (by ATAC-seq) and HIV-1-chromtain interaction (by 4C-seq), we identified enrichment of ETS, RUNT, STAT, and ZNF transcription factor binding that may mediate HIV-1-host chromatin interactions. Our study found that HIV-1 promoter activity increased host chromatin accessibility, increased HIV-1-host chromatin interactions in an integration site dependent manner, within the existing chromatin boundaries without impacting broader host chromatin structure.
2023-05-01 | GSE229926 | GEO
Project description:Human APOBEC3 enzymes are a family of single-stranded (ss)DNA and RNA cytidine deaminases that act as part of the intrinsic immunity against viruses and retroelements. APOBEC3s deaminate cytosine to form uracil which can functionally inactivate or cause degradation of viral or retroelement genomes. In addition, APOBEC3 proteins have deamination independent anti-viral activity and aberrant regulation of APOBEC3 expression can result in the deamination and mutagenesis of the genome contributing to cancer initiation and evolution. To further understand their cellular roles, we used affinity purification mass spectrometry (AP-MS) to determine the protein-protein interaction (PPI) network for the human APOBEC3 enzymes and uncovered a diverse number of protein-protein and protein-RNA mediated interactions. PPIs with the Prefoldin family of protein folding chaperones were identified for APOBEC3B, APOBEC3D, and APOBEC3F. The APOBEC3B and prefoldin 5 (PFD5) interaction disrupted the ability of PFD5 to induce degradation of the oncogene cMyc, implicating a deamination independent contribution of APOBEC3B to cancer. Altogether, the results uncover novel functions and interactions of the APOBEC3 family and suggest that they may have fundamental roles in cellular RNA biology, their roles are not redundant, and there is a deamination independent influence on cancer.
2024-04-16 | PXD044275 | Pride
Project description:Understanding the complexity of the long-lived HIV reservoir during antiretroviral therapy (ART) remains a major impediment for HIV cure research. To address this, we developed single-cell viral ASAPseq to precisely define the unperturbed peripheral blood HIV-infected memory CD4+ T cell reservoir from antiretroviral treated people living with HIV (ART-PLWH) via the presence of integrated accessible proviral DNA in concert with epigenetic and cell surface protein profiling. We identified profound reservoir heterogeneity within and between ART-PLWH, characterized by novel and known surface markers within total and individual memory CD4+ T cell subsets. We further uncovered novel epigenetic profiles and transcription factor motifs enriched in HIV-infected cells that suggest infected cells with accessible provirus, irrespective of reservoir distribution, are poised for reactivation during ART treatment. Together, our findings reveal the extensive inter- and intrapersonal cellular heterogeneity of the HIV reservoir, and establish an initial multiomic atlas to develop targeted reservoir elimination strategies.
2022-10-21 | GSE199727 | GEO
Project description:Although HIV-1 integration sites are considered to favor active transcription units in the human genome, high-resolution analysis of individual HIV-1 integration sites have shown that the virus can integrate in a variety of host genomic locations, including non-genic regions, challenging the traditional understanding of HIV-1 integration site selection. Here, we showed that HIV-1 targets R-loops, a genomic structure made up of DNA–RNA hybrids, for integration. HIV-1 initiates the formation of R-loops in both genic and non-genic regions of the host genome and preferentially integrates into regions of HIV-1-induced R-loops. Using a cell model that can independently control transcriptional activity and R-loop formation, we demonstrated that the presence of R-loops, regardless of transcriptional activity, directs HIV-1 integration targeting sites. We also found that HIV-1 integrase proteins bind to the host genomic R-loops. These findings provide fundamental insights into the mechanisms of retroviral integration and the new strategies of antiretroviral therapy against HIV-1 latent infection.
2024-11-05 | GSE281027 | GEO