Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regulation of transcriptomic profile by ZL0580 and JQ1

ABSTRACT: Epigenetic suppression and durable silencing of HIV represent a promising strategy to achieve ART-free remission, consistent with the “block and lock” HIV cure paradigm. BRD4 is a host epigenetic reader and plays a critical role in HIV transcriptional regulation. We previously identified ZL0580, a first-in-class BRD4-selective small molecule that epigenetically suppresses HIV, whereas the pan-BET/BRD4 inhibitor JQ1 activates HIV transcription. The present study utilizes RNA-Sequencing (RNA-Seq) to examine the impact of ZL0580 and JQ1 on transcriptomic profile in the latently HIV-infected J-Lat cells (Clone 10.6). In summary, ZL0580 induces a transcriptomic profile opposing to that induced by JQ1, which is highly consistent the opposing effects of the two compounds on HIV transcription and latency.

ORGANISM(S): Homo sapiens

PROVIDER: GSE315344 | GEO | 2026/01/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE315344_HaitaoHu_raw_counts.xlsx	Xlsx

Items per page:

1 - 2 of 2

Similar Datasets

RBM39 organizes an m⁶A-dependent silencing complex to degrade Tat mRNA and maintain HIV-1 latency

Project description:Given the pivotal role of Tat in HIV-1 latency, we performed RNA pull-down assays in latently HIV-1-infected J-Lat 10.6 cells using biotinylated RNA probes (including a control RNA probe and a Tat-specific RNA probe) . Cell lysates were incubated with streptavidin agarose resin pre-bound to Tat RNA probes, and the enriched Tat RNA-binding proteins were separated by SDS-PAGE and analyzed by liquid chromatography mass spectrometry (LC-MS/MS)

2025-10-31 | PXD064834 | Pride

New BRD4-inhibitor quinoline compound targets a distinct latent HIV-1 reservoir for re-activation from canonical “shock” drugs

Project description:Upon HIV-1 infection, a reservoir of latently infected resting T cells prevents the eradication of the virus from patients. To achieve complete depletion, the existing virus-suppressing antiretroviral therapy must be combined with drugs that reactivate the dormant viruses. We previously described a novel chemical scaffold compound, MMQO (8-methoxy-6-methylquinolin-4-ol) that is able to reactivate viral transcription in J-Lat T cell model of latency through an unknown mechanism. Here we demonstrate that MMQO activates HIV-1 in ex vivo latently infected primary CD4 T cells, where it synergizes with the PKC agonist prostratin. Gene expression microarray analysis in Jurkat cells indicated that MMQO treatment results in robust immunosuppression, affects cell proliferation by rapidly diminishing expression of the transcription factor c-Myc, and causes the dysregulation of acetylation sensitive genes. These hallmarks indicated that MMQO mimics acetylated lysines of core histones and might function as a bromodomain and extraterminal domain protein family inhibitor (BETi). MMQO functionally mimics the effects of JQ1, a well-known BETi. We confirmed that MMQO interacts with the BET family bromodomain BRD4. Utilizing MMQO and JQ1, we demonstrate how the inhibition of BRD4 targets a distinct subset of latently integrated barcoded proviruses from those targeted by HDAC inhibitors or PKC pathway agonists. Thus, the scaffold compound MMQO is a new member of the BET family inhibitors, which due to its minimalistic structure holds promise for further optimization for increased affinity and specificity for distinct bromodomain family members and could potentially be of use against a variety of diseases, including HIV.

2018-06-21 | GSE100289 | GEO

J-Lat 10.6 cell line treated with either DMSO, 10μM compound 4, or 10μM compound 16 for 24 h.

Project description:Human immunodeficiency virus (HIV) still remains a major global public health issue. Combination antiretroviral therapy (ART) is effective to reduce the morbidity and mortality of HIV infected patients. However, ART is unable to eradicate HIV due to the establishment of long-lived and proliferating HIV latently infected cells. Once ART is stopped, these cells will drive resurgence of the infection. Hence, ART in combination with HIV latency reversing agents (LRAs), which target signaling pathways involved in HIV transcription, has become an approach to target and eliminate HIV latency. Here, we identified two compounds with novel structures possessing HIV latency reversing activity. They are named compound 4 and 16, respectively. To understand their underlying mechanism, we carried out RNA-seq for J-Lat 10.6 cells treated with either DMSO, 10μM compound 4, or 10μM compound 16 for 24 h.

2026-01-14 | GSE303365 | GEO

Oncolytic reactivation of KSHV as a therapeutic approach for primary effusion lymphoma: RNA-sequencing of PEL cell lines during KSHV reactivation

Project description:Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma caused by Kaposi’s sarcoma-associated herpesvirus infection, which is most commonly seen in HIV-positive patients. Induction of HIV reactivation by external stimuli in the presence of highly active anti-retroviral therapy (HAART) has been examined for its efficacy to eradicate latently infected HIV. Similary, lytic activation of viruses from latently infected tumor cells with anti-cancer drugs represents an effective strategy of anti-neoplastic therapy, through the induction of oncolysis by viral replication, stimulation of immune responses to the viral lytic antigens, and intrinsic effects of cancer drugs. Here we examined the combination of PEP005 with epigenetic drugs as a rational therapeutic strategy to target both in AIDS-associated KSHV-mediated malignancies. JQ1, a bromodomain and extra terminal protein (BET) inhibitor, in combination with a FDA-approved drug, PEP005, not only robustly induced KSHV lytic replication, but also inhibited IL-6 and VEGF production from PEL cells. This combination has been proposed for use in reactivation of HIV from latently infected T-cells, and the same combination and dosage inhibited PEL growth in vitro and delayed tumor growth in a PEL xenograft tumor model. Downstream activation of NF-B by PEP005 combined with sequestration of bromodomain-containing protein 4 (BRD4) by JQ1 robustly increased occupancy of RNA polymerase II onto the KSHV genome. RNA-sequencing analysis further revealed cellular targets of PEP005, JQ1, and the synergistic effects of both. We suggest that the combination of PEP005 with JQ1 should be considered as a rational therapeutic approach for HIV-associated PEL.

2017-11-03 | GSE89478 | GEO

A modular CRISPR screen identifies individual and combination pathways contributing to HIV-1 latency

Project description:The goal of this CRISPR-based screen (Latency HIV-CRISPR) is to identify HIV-1 latency factors by evaluating multiple pathways simultaneously. Here are Illumina sequencing data and counts files from a Latency HIV-CRISPR screen using a custom guide RNA library targeting human epigenome genes (HuEpi). The Latency HIV-CRISPR screens described here were performed in clonal ZAP knockout J-Lat 10.6 (PMID: 12682019) or J-Lat 5A8 (PMID: 24204950) cells lines as ZAP inhibition of the HIV-CRISPR vector has been previously described (PMID: 30520725). The screens were performed in the presence or absence of AZD5582, a SMAC mimetic and latency reversal agent, in order to identify factors that are dependent and independent of this transcriptional activator.

2022-12-21 | GSE213995 | GEO

Kinetics after JQ1 treatment in liver cancer cell

Project description:Analysis of global gene expression after BRD4 inhibition by JQ1 in liver cancer cell lines SK-Hep1 Total RNA obtained from human liver cancer cell line SK-Hep1 cells after treatment of JQ1

2016-07-20 | E-GEOD-75908 | biostudies-arrayexpress

A two-color haploid genetic screen identifies novel host factors involved in HIV-1 latency

Project description:To identify novel host factors as putative targets to reverse HIV-1 latency, we performed an insertional mutagenesis genetic screen in a latently HIV-1-infected pseudohaploid KBM7 cell line (Hap-Lat). Following mutagenesis, insertions were mapped to the genome, and bioinformatic analysis resulted in the identification of 69 candidate host genes involved in maintaining HIV-1 latency.

2021-11-22 | GSE189314 | GEO

Kinetics after JQ1 treatment in liver cancer cell

Project description:Analysis of global gene expression after BRD4 inhibition by JQ1 in liver cancer cell lines SK-Hep1

2016-07-20 | GSE75908 | GEO

Syngergistic Effect of JQ1 and Rapamycin for Treatment of Human Osteosarcoma

Project description:Bromodomain and extra terminal domain (BET) proteins are important epigenetic regulators facilitating the transcription of genes in chromatin areas linked to acetylated histones. JQ1, a BET protein inhibitor, has antiproliferative activity against many cancers, mainly through inhibition of c-MYC and upregulation of p21. In this research, we investigated the use of JQ1 for human osteosarcoma (OS) treatment. JQ1 significantly inhibited the proliferation and survival of OS cells inducing G1 cell cycle arrest, premature senescence, but little effect on apoptosis. Interestingly, c-MYC protein levels in JQ1-treated cells remained unchanged, whereas the upregulation of p21 protein was still observable. Although effective in vitro, JQ1 alone failed to reduce the size of the MNNG/HOS xenografts in immunocompromised mice. To overcome the resistance of OS cells to JQ1 treatment, we combined JQ1 with rapamycin, an mTOR inhibitor. JQ1 and rapamycin synergistically inhibited the growth and survival of OS cells in vitro and in vivo. We also identified that RUNX2 is a direct target of BRD4 inhibition by JQ1 in OS cells. Chromatin immunoprecipitation (ChIP) showed that enrichment of BRD4 protein around RUNX2 transcription start sites diminished with JQ1 treatment in MNNG/HOS cells. Overexpression of RUNX2 protected JQ1-sensitive OS cells from the effect of JQ1, and siRNA-mediated inhibition of RUNX2 sensitized the same cells to JQ1. In conclusion, our findings suggest that JQ1, in combination with rapamycin, is an effective chemotherapeutic option for OS treatment. We also show that inhibition of RUNX2 expression by JQ1 partly explains antiproliferative activity of JQ1 in OS cells. MNNG/HOS cells treated with 7.5mM JQ1, 12.5nM Rapamycin or both were used for RNA extraction and hybridization on Affymetrix microarrays. We compared these microarray samples with the corresponding control (treated with DMSO).

2015-05-01 | E-GEOD-57203 | biostudies-arrayexpress

RNA-seq of human melanoma cancer cell line A375 treated with BET inhibitor JQ1 against untreated control

Project description:To set the relevance of BRD4 as repressor, we performed gene expression profile by RNA-seq in A375 treated with BETi JQ1 to identify potential BRD4 target genes.

2021-03-31 | E-MTAB-8649 | biostudies-arrayexpress