ArticleScience advances2021
BRD4 methylation by the methyltransferase SETD6 regulates selective transcription to control mRNA translation.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- Article
- Transcriptional and epigenetic reprogramming, lineage plasticity and therapy resistance in prostate cancer.Journal of the National Cancer Center · 2026Review
- E2F1 K117 methylation by SETD6 disrupts BRD4-E2F1 binding and modulates E2F1 chromatin binding and gene regulation in prostate cancer cells.Nucleic acids research · 2026Article
- Mechanisms of Substrate Recognition by the Multispecific Protein Lysine Methyltransferase SETD6.Life (Basel, Switzerland) · 2025Article
- SETD6 mediates selective interaction and genomic occupancy of BRD4 and MITF in melanoma cells.NAR cancer · 2025Article
- Untargeted Diversity-Oriented Synthesis for the Discovery of New Antitumor Agents: An Integrated Approach of Inverse Virtual Screening, Bioinformatics, and Omics for Target Deconvolution.Journal of medicinal chemistry · 2025Article
- Salvianic acid A promotes osteogenic differentiation of bone marrow mesenchymal stem cells in senile osteoporosis through bromodomain-containing protein 4/Ariadne RBR E3 ubiquitin-protein ligase 1/Rubicon axis.Journal of traditional and complementary medicine · 2025Article
- Orchestrating epigenetics: a comprehensive review of the methyltransferase SETD6.Experimental & molecular medicine · 2025Review
- Distinct specificities of the HEMK2 protein methyltransferase in methylation of glutamine and lysine residues.Protein science : a publication of the Protein Society · 2024Article
- Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- Methylation of BRD4 by PRMT1 regulates BRD4 phosphorylation and promotes ovarian cancer invasion.Cell death & disease · 2023Article
- Methylation across the central dogma in health and diseases: new therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- Mechanisms of Interaction between Enhancers and Promoters in ThreeInternational journal of molecular sciences · 2023Review
- Investigating the functional role of SETD6 in lung adenocarcinoma.BMC cancer · 2023Article
- Optimizing purification and activity assays of N-terminal methyltransferase complexes.Methods in enzymology · 2023Article
- Regulation of programmed cell death by Brd4.Cell death & disease · 2022Review
- Arginine methylation of BRD4 by PRMT2/4 governs transcription and DNA repair.Science advances · 2022Article
- SETD6 Regulates E2-Dependent Human Papillomavirus Transcription.Journal of virology · 2022Article
- Retinoblastoma protein as an intrinsic BRD4 inhibitor modulates small molecule BET inhibitor sensitivity in cancer.Nature communications · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcriptional coactivator BRD4 has a fundamental role in transcription regulation and thus became a promising epigenetic therapeutic candidate to target diverse pathologies. However, the regulation of BRD4 by posttranslational modifications has been largely unexplored. Here, we show that BRD4 is methylated on chromatin at lysine-99 by the protein lysine methyltransferase SETD6. BRD4 methylation negatively regulates the expression of genes that are involved in translation and inhibits total mRNA translation in cells. Mechanistically, we provide evidence that supports a model where BRD4 methylation by SETD6 does not have a direct role in the association with acetylated histone H4 at chromatin. However, this methylation specifically determines the recruitment of the transcription factor E2F1 to selected target genes that are involved in mRNA translation. Together, our findings reveal a previously unknown molecular mechanism for BRD4 methylation-dependent gene-specific targeting, which may serve as a new direction for the development of therapeutic applications.
Indexed as
Identifiers
What OpenQuestion holds
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.