ArticleStem cells and development2015
Nanog requires BRD4 to maintain murine embryonic stem cell pluripotency and is suppressed by bromodomain inhibitor JQ1 together with Lefty1.
Article in Stem cells and development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 56 citations in OpenAlex.
- Trial
- Article
- Bromodomain-Driven Regulation of Stem Cells: A Potential Target for Cancer Therapeutic Intervention.Stem cell reviews and reports · 2026Review
- Bromodomain and extraterminal protein inhibitor JQ1 induces maturation arrest and disrupts the cytoplasmic organization in mouse oocytes under in vitro conditions.Scientific reports · 2025Article
- FGF2 supports NANOG expression via pyruvate dehydrogenase-dependent histone acetylation under low oxygen conditions.Frontiers in cell and developmental biology · 2025Article
- BET activity plays an essential role in control of stem cell attributes in Xenopus.Development (Cambridge, England) · 2024Article
- Histone deacetylases maintain expression of the pluripotent gene network via recruitment of RNA polymerase II to coding and noncoding loci.Genome research · 2024Article
- Digital Phenotyping for Mood Disorders: Methodology-Oriented Pilot Feasibility Study.Journal of medical Internet research · 2023Article
- Bromodomain (BrD) Family Members as Regulators of Cancer Stemness-A Comprehensive Review.International journal of molecular sciences · 2023Review
- R132H IDH1 sensitizes glioma to the antiproliferative and cytotoxic effects of BET inhibition.Journal of cancer research and clinical oncology · 2022Article
- Article
- The association between bromodomain proteins and cancer stemness in different solid tumor types.International journal of cancer · 2022Article
- BET proteins are essential for the specification and maintenance of the epiblast lineage in mouse preimplantation embryos.BMC biology · 2022Article
- Dicer promotes genome stability via the bromodomain transcriptional co-activator BRD4.Nature communications · 2022Article
- Histone Acetyltransferases and Stem Cell Identity.Cancers · 2021Review
- Chromatin and Epigenetic Rearrangements in Embryonic Stem Cell Fate Transitions.Frontiers in cell and developmental biology · 2021Review
- Combined treatment with CBP and BET inhibitors reverses inadvertent activation of detrimental super enhancer programs in DIPG cells.Cell death & disease · 2020Article
- Review
- Interference with the bromodomain epigenome readers drives p21 expression and tumor senescence.Cancer letters · 2019Article
- Efficient Differentiation of Mouse Induced Pluripotent Stem Cells into Alveolar Epithelium Type II with a BRD4 Inhibitor.Stem cells international · 2019Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Embryonic stem cells (ESCs) are maintained in an undifferentiated state through expression of the core transcriptional factors Nanog, Oct4, and Sox2. However, the epigenetic regulation of pluripotency is poorly understood. Differentiation of ESCs is accompanied by a global reduction of panacetylation of histones H3 and H4 suggesting that histone acetylation plays an important role in maintenance of ESC pluripotency. Acetylated lysine residues on histones are read by members of the bromodomain family that includes BET (bromodomain and extraterminal domain) proteins for which highly potent and selective inhibitors have been developed. In this study we demonstrate that the pan-BET bromodomain inhibitor JQ1 induces rapid spontaneous differentiation of murine ESCs by inducing marked transcriptional downregulation of Nanog as well as the stemness markers Lefty1 and Lefty2, but not Myc, often used as a marker of BET inhibitor activity in cancer. We show that the effects of JQ1 are recapitulated by knockdown of the BET family member BRD4 implicating this protein in Nanog regulation. These data are also supported by chromatin immunoprecipitation experiments which confirm BRD4 binding at the Nanog promoter that is known to require acetylation by the histone acetyltransferase MOF for transcriptional activity. In further support of our findings, we show that JQ1 antagonizes the stem cell-promoting effects of the histone deacetylase inhibitors sodium butyrate and valproic acid. Our data suggest that BRD4 is critical for the maintenance of ESC pluripotency and that this occurs primarily through the maintenance of Nanog expression.
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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.