ArticleEMBO reports2017
Brd4-Brd2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification.
Article in EMBO reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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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.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Dysregulation of the BRD2-FGF17 Signal Pathway Induces Abnormal Forebrain Development Associated with Schizophrenia.Neuroscience bulletin · 2026Article
- Bromodomain-Driven Regulation of Stem Cells: A Potential Target for Cancer Therapeutic Intervention.Stem cell reviews and reports · 2026Review
- Divergent destinies: insights into the molecular mechanisms underlying EPI and PE fate determination.Life science alliance · 2025Review
- BET activity plays an essential role in control of stem cell attributes in Xenopus.Development (Cambridge, England) · 2024Article
- Article
- Regulation of Cell Plasticity by Bromodomain and Extraterminal Domain (BET) Proteins: A New Perspective in Glioblastoma Therapy.International journal of molecular sciences · 2023Review
- BET proteins are essential for the specification and maintenance of the epiblast lineage in mouse preimplantation embryos.BMC biology · 2022Article
- Zebrafish ParalogsJournal of developmental biology · 2021Article
- BRD4 orchestrates genome folding to promote neural crest differentiation.Nature genetics · 2021Article
- Brd2/4 and Myc regulate alternative cell lineage programmes during early osteoclast differentiation in vitro.iScience · 2021Article
- The Functions of BET Proteins in Gene Transcription of Biology and Diseases.Frontiers in molecular biosciences · 2021Review
- Functional Diversification of SRSF Protein Kinase to Control Ubiquitin-Dependent Neurodevelopmental Signaling.Developmental cell · 2020Article
- lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation.Nature cell biology · 2020Article
- Phosphoproteomics identifies a bimodal EPHA2 receptor switch that promotes embryonic stem cell differentiation.Nature communications · 2020Article
- Bromodomain and extra-terminal domain (BET) proteins regulate melanocyte differentiation.Epigenetics & chromatin · 2020Article
- Bromodomain Protein BRD4 Is Essential for Hair Cell Function and Survival.Frontiers in cell and developmental biology · 2020Article
- Time series modeling of cell cycle exit identifies Brd4 dependent regulation of cerebellar neurogenesis.Nature communications · 2019Article
- JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states.Epigenetics · 2018Article
- Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival.Nature communications · 2017Article
- Brd4-Brd2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification.EMBO reports · 2017Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Pluripotent stem cells (PSCs) hold great clinical potential, as they possess the capacity to differentiate into fully specialised tissues such as pancreas, liver, neurons and cardiac muscle. However, the molecular mechanisms that coordinate pluripotent exit with lineage specification remain poorly understood. To address this question, we perform a small molecule screen to systematically identify novel regulators of the Smad2 signalling network, a key determinant of PSC fate. We reveal an essential function for BET family bromodomain proteins in Smad2 activation, distinct from the role of Brd4 in pluripotency maintenance. Mechanistically, BET proteins specifically engage Nodal gene regulatory elements (NREs) to promote Nodal signalling and Smad2 developmental responses. In pluripotent cells, Brd2-Brd4 occupy NREs, but only Brd4 is required for pluripotency gene expression. Brd4 downregulation facilitates pluripotent exit and drives enhanced Brd2 NRE occupancy, thereby unveiling a specific function for Brd2 in differentiative Nodal-Smad2 signalling. Therefore, distinct BET functionalities and Brd4-Brd2 isoform switching at NREs coordinate pluripotent exit with lineage specification.
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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.