Virus Dataset Detail

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Dataset Information
Accession GSE211651
Status 2023/3/23
Title Enhancing HIV-1 latency reversal through regulating the elongating RNA Pol II pause-release by a small-molecule disruptor of PAF1C
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing;Genome binding/occupancy profiling by high throughput sequencing;Other
Summary The polymerase-associated factor 1 complex (PAF1C) is a key, post-initiation transcriptional regulator of both promoter-proximal pausing and productive elongation catalyzed by RNA Pol II and is also involved in transcriptional repression of viral gene expression during human immunodeficiency virus–1 (HIV-1) latency. Using a molecular docking–based compound screen in silico and global sequencing–based candidate evaluation in vivo, we identified a first-in-class, small-molecule inhibitor of PAF1C (iPAF1C) that disrupts PAF1 chromatin occupancy and induces global release of promoter-proximal paused RNA Pol II into gene bodies. Transcriptomic analysis revealed that iPAF1C treatment mimics acute PAF1 subunit depletion and impairs RNA Pol II pausing at heat shock–down-regulated genes. Furthermore, iPAF1C enhances the activity of diverse HIV-1 latency reversal agents both in cell line latency models and in primary cells from persons living with HIV-1. In sum, this study demonstrates that efficient disruption of PAF1C by a first-in-class, small-molecule inhibitor may have therapeutic potential for improving current HIV-1 latency reversal strategies.
Samples
GSM ID Sample info Characteristics Description
GSM6482041 ChIP-seq_Input_HCT116 tissue:colon; cell line:HCT116; cell type:colorectal carcinoma; genotype:WT; treatment:untreated; chip antibody:none -
GSM6482042 ChIP-seq_PolII_HCT116_DMSO tissue:colon; cell line:HCT116; cell type:colorectal carcinoma; genotype:WT; treatment:DMSO; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482043 ChIP-seq_PolII_HCT116_iPAF1C tissue:colon; cell line:HCT116; cell type:colorectal carcinoma; genotype:WT; treatment:iPAF1C 20uM; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482044 ChIP-seq_PolII_HCT116_NUiPAF-22 tissue:colon; cell line:HCT116; cell type:colorectal carcinoma; genotype:WT; treatment:NUiPAF-22 20uM; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482045 ChIP-seq_PolII_HCT116_shPAF1 tissue:colon; cell line:HCT116; cell type:colorectal carcinoma; genotype:PAF1 knockdown; treatment:untreated; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482046 ChIP-seq_Input_DLD1 tissue:colon; cell line:DLD-1; cell type:colorectal adenocarcinoma; genotype:WT; treatment:untreated; chip antibody:none -
GSM6482047 ChIP-seq_PAF1_DLD1_DMSO tissue:colon; cell line:DLD-1; cell type:colorectal adenocarcinoma; genotype:WT; treatment:untreated; chip antibody:PAF1 (D9G9X, Rabbit mAb). -
GSM6482048 ChIP-seq_PAF1_DLD1_iPAF1C tissue:colon; cell line:DLD-1; cell type:colorectal adenocarcinoma; genotype:WT; treatment:iPAF1C 20uM; chip antibody:PAF1 (D9G9X, Rabbit mAb). -
GSM6482049 ChIP-seq_PAF1_DLD1_NuiPAF-22R-26 tissue:colon; cell line:DLD-1; cell type:colorectal adenocarcinoma; genotype:WT; treatment:NUiPAF-22 20uM; chip antibody:PAF1 (D9G9X, Rabbit mAb). -
GSM6482050 ChIP-seq_Input_PAF1AID-DLD1 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:untreated; chip antibody:none -
GSM6482051 ChIP-seq_PolII_PAF1AID-DLD1_DMSO_Rep1 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:DMSO; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482052 ChIP-seq_PolII_PAF1AID-DLD1_DMSO_Rep2 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:DMSO; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482053 ChIP-seq_PolII_PAF1AID-DLD1_DMSO_Rep3 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:DMSO; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482054 ChIP-seq_PolII_PAF1AID-DLD1_iPAF1C_Rep1 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:iPAF1C 20uM; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482055 ChIP-seq_PolII_PAF1AID-DLD1_iPAF1C_Rep2 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:iPAF1C 20uM; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482056 ChIP-seq_PolII_PAF1AID-DLD1_Auxin tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:Auxin 500uM; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482057 ChIP-seq_PolII_PAF1AID-DLD1_NT tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:untreated; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482058 PRO-seq_DLD1_iPAF1C tissue:colon; cell line:DLD-1; cell type:colorectal adenocarcinoma; genotype:WT; treatment:iPAF1C 20uM -
GSM6482059 PRO-seq_DLD1_iPAF1C_HS tissue:colon; cell line:DLD-1; cell type:colorectal adenocarcinoma; genotype:WT; treatment:iPAF1C 20uM, heat shock -
GSM6482060 PRO-seq_DLD1_DMSO tissue:colon; cell line:DLD-1; cell type:colorectal adenocarcinoma; genotype:WT; treatment:DMSO -
GSM6482061 PRO-seq_DLD1_DMSO_HS tissue:colon; cell line:DLD-1; cell type:colorectal adenocarcinoma; genotype:WT; treatment:DMSO, heat shock -
GSM6482062 PRO-seq_DLD1_shPAF1 tissue:colon; cell line:DLD-1; cell type:colorectal adenocarcinoma; genotype:PAF1 knockdown; treatment:untreated -
GSM6482063 PRO-seq_DLD1_shPAF1_HS tissue:colon; cell line:DLD-1; cell type:colorectal adenocarcinoma; genotype:PAF1 knockdown; treatment:heat shock -
GSM6482064 RNA-seq_PAF1AID-DLD1_iPAF1C_Rep1 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:iPAF1C 20uM -
GSM6482065 RNA-seq_PAF1AID-DLD1_iPAF1C_Rep2 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:iPAF1C 20uM -
GSM6482066 RNA-seq_PAF1AID-DLD1_iPAF1C_Rep3 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:iPAF1C 20uM -
GSM6482067 RNA-seq_PAF1AID-DLD1_Auxin_Rep1 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:Auxin 500uM -
GSM6482068 RNA-seq_PAF1AID-DLD1_Auxin_Rep2 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:Auxin 500uM -
GSM6482069 RNA-seq_PAF1AID-DLD1_Auxin_Rep3 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:Auxin 500uM -
GSM6482070 RNA-seq_PAF1AID-DLD1_DMSO_Rep1 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:DMSO -
GSM6482071 RNA-seq_PAF1AID-DLD1_DMSO_Rep2 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:DMSO -
GSM6482072 RNA-seq_PAF1AID-DLD1_DMSO_Rep3 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:DMSO -
GSM6482073 RNA-seq_PAF1AID-DLD1_NT_Rep1 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:untreated -
GSM6482074 RNA-seq_PAF1AID-DLD1_NT_Rep2 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:untreated -
GSM6482075 RNA-seq_PAF1AID-DLD1_NT_Rep3 tissue:colon; cell line:DLD-1_PAF1AID; cell type:colorectal adenocarcinoma; genotype:PAF1-AID; treatment:untreated -
GSM6482076 ChIP-seq_PolII_JLAT_DMSO_HIV tissue:peripheral blood; cell line:J-LAT 5a8; cell type:T lymphoblast; genotype:clone 5a8; treatment:DMSO; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482077 ChIP-seq_PolII_JLAT_iPAF1C_JQ1_HIV tissue:peripheral blood; cell line:J-LAT 5a8; cell type:T lymphoblast; genotype:clone 5a8; treatment:iPAF1C+JQ1; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482078 ChIP-seq_PolII_JLAT_JQ1_HIV tissue:peripheral blood; cell line:J-LAT 5a8; cell type:T lymphoblast; genotype:clone 5a8; treatment:JQ1; chip antibody:Rpb1 NTD (D8L4Y) -
GSM6482079 ChIP-seq_PolII_JLAT_shPAF1_JQ1_HIV tissue:peripheral blood; cell line:J-LAT 5a8; cell type:T lymphoblast; genotype:clone 5a8, PAF1 knockdown; treatment:JQ1; chip antibody:Rpb1 NTD (D8L4Y) -
Platform GPL18573  GPL24676  : Illumina NextSeq 500 (Homo sapiens);Illumina NovaSeq 6000 (Homo sapiens)
Literature 36888719  
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* p<0.05 ** p<0.01