ArticleEpigenetics2018
JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states.
Article in Epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- BRD2 upregulation as a pan-cancer adaptive resistance mechanism to BET inhibition.Cellular & molecular biology letters · 2026Article
- Overcoming BET-inhibitor JQ1 resistance in aggressive non-small cell lung cancer by inducing ferroptosis via inhibition of the BRD2-FTH1 axis.The FEBS journal · 2025Article
- The BRD4-nucleosome interaction is enhanced modestly and non-selectively by histone acetylation.Nucleic acids research · 2025Article
- BRD2 Upregulation as a Pan-Cancer Adaptive Resistance Mechanism to BET Inhibition.bioRxiv : the preprint server for biology · 2025Article
- SARS-CoV-2 E protein interacts with BRD2 and BRD4 SEED domains and alters transcription in a different way than BET inhibition.Cellular and molecular life sciences : CMLS · 2024Article
- Investigation of the impact of bromodomain inhibition on cytoskeleton stability and contraction.Cell communication and signaling : CCS · 2024Article
- Defining super-enhancers by highly ranked histone H4 multi-acetylation levels identifies transcription factors associated with glioblastoma stem-like properties.BMC genomics · 2023Article
- Epigenetic mechanisms to propagate histone acetylation by p300/CBP.Nature communications · 2023Article
- MYC activation impairs cell-intrinsic IFNγ signaling and confers resistance to anti-PD1/PD-L1 therapy in lung cancer.Cell reports. Medicine · 2023Article
- Factors and Mechanisms That Influence Chromatin-Mediated Enhancer-Promoter Interactions and Transcriptional Regulation.Cancers · 2022Review
- Functional inhibition of c-Myc using novel inhibitors identified through "hot spot" targeting.The Journal of biological chemistry · 2022Article
- BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2.Nature cell biology · 2022Article
- Investigating crosstalk between H3K27 acetylation and H3K4 trimethylation in CRISPR/dCas-based epigenome editing and gene activation.Scientific reports · 2021Article
- A novel inhibitor L755507 efficiently blocks c-Myc-MAX heterodimerization and induces apoptosis in cancer cells.The Journal of biological chemistry · 2021Article
- Cistrome analysis of YY1 uncovers a regulatory axis of YY1:BRD2/4-PFKP during tumorigenesis of advanced prostate cancer.Nucleic acids research · 2021Article
- Decoding regulatory structures and features from epigenomics profiles: A Roadmap-ENCODE Variational Auto-Encoder (RE-VAE) model.Methods (San Diego, Calif.) · 2021Article
- BRD4 methylation by the methyltransferase SETD6 regulates selective transcription to control mRNA translation.Science advances · 2021Article
- Reprogramming of the FOXA1 cistrome in treatment-emergent neuroendocrine prostate cancer.Nature communications · 2021Article
- The BET family in immunity and disease.Signal transduction and targeted therapy · 2021Review
- Deep learning approach for predicting functional Z-DNA regions using omics data.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bromodomain and extra-terminal domain (BET) proteins are promising drug targets for cancer and immune diseases. However, BET inhibition effects have been studied more in the context of bromodomain-containing protein 4 (BRD4) than BRD2, and the BET protein association to histone H4-hyperacetylated chromatin is not understood at the genome-wide level. Here, we report transcription start site (TSS)-resolution integrative analyses of ChIP-seq and transcriptome profiles in human non-small cell lung cancer (NSCLC) cell line H23. We show that di-acetylation at K5 and K8 of histone H4 (H4K5acK8ac) co-localizes with H3K27ac and BRD2 in the majority of active enhancers and promoters, where BRD2 has a stronger association with H4K5acK8ac than H3K27ac. Although BET inhibition by JQ1 led to complete reduction of BRD2 binding to chromatin, only local changes of H4K5acK8ac levels were observed, suggesting that recruitment of BRD2 does not influence global histone H4 hyperacetylation levels. This finding supports a model in which recruitment of BET proteins via histone H4 hyperacetylation is predominant over hyperacetylation of histone H4 by BET protein-associated acetyltransferases. In addition, we found that a remarkable number of BRD2-bound genes, including MYC and its downstream target genes, were transcriptionally upregulated upon JQ1 treatment. Using BRD2-enriched sites and transcriptional activity analysis, we identified candidate transcription factors potentially involved in the JQ1 response in BRD2-dependent and -independent manner.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.