ArticleJournal of cellular physiology2020
The epigenetic reader Brd4 is required for osteoblast differentiation.
Article in Journal of cellular physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- BRD2 is a transcriptional coactivator of Smad3 in mediating TGF-β tumor suppressive responses.Oncogene · 2026Article
- FOXJ3 drives mesenchymal stem cell osteogenic differentiation via the Wnt/β‑catenin pathway: A novel regulator implicated in osteoporosis.Molecular medicine reports · 2026Article
- BRD4 binds to active cranial neural crest enhancers to regulate RUNX2 activity during osteoblast differentiation.Development (Cambridge, England) · 2024Article
- Protein arginine methyltransferases PRMT1, PRMT4/CARM1 and PRMT5 have distinct functions in control of osteoblast differentiation.Bone reports · 2023Article
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- BET in hematologic tumors: Immunity, pathogenesis, clinical trials and drug combinations.Genes & diseases · 2023Review
- Super enhancers targeting ZBTB16 in osteogenesis protect against osteoporosis.Bone research · 2023Article
- The epigenetic regulator BRD4 is required for myofibroblast differentiation of knee fibroblasts.Journal of cellular biochemistry · 2023Article
- MicroRNA-101a enhances trabecular bone accrual in male mice.Scientific reports · 2022Article
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- Lysine-Specific Demethylase 1 (LSD1) epigenetically controls osteoblast differentiation.PloS one · 2022Article
- Pulmonary hypertension: Linking inflammation and pulmonary arterial stiffening.Frontiers in immunology · 2022Review
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- Genetic background dependent modifiers of craniosynostosis severity.Journal of structural biology · 2020Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Transcription networks and epigenetic mechanisms including DNA methylation, histone modifications, and noncoding RNAs control lineage commitment of multipotent mesenchymal progenitor cells. Proteins that read, write, and erase histone tail modifications curate and interpret the highly intricate histone code. Epigenetic reader proteins that recognize and bind histone marks provide a crucial link between histone modifications and their downstream biological effects. Here, we investigate the role of bromodomain-containing (BRD) proteins, which recognize acetylated histones, during osteogenic differentiation. Using RNA-sequencing (RNA-seq) analysis, we screened for BRD proteins (n = 40) that are robustly expressed in MC3T3 osteoblasts. We focused functional follow-up studies on Brd2 and Brd4 which are highly expressed in MC3T3 preosteoblasts and represent "bromodomain and extra terminal domain" (BET) proteins that are sensitive to pharmacological agents (BET inhibitors). We show that small interfering RNA depletion of Brd4 has stronger inhibitory effects on osteoblast differentiation than Brd2 loss as measured by osteoblast-related gene expression, extracellular matrix deposition, and alkaline phosphatase activity. Similar effects on osteoblast differentiation are seen with the BET inhibitor +JQ1, and this effect is reversible upon its removal indicating that this small molecule has no lasting effects on the differentiation capacity of MC3T3 cells. Mechanistically, we find that Brd4 binds at known Runx2 binding sites in promoters of bone-related genes. Collectively, these findings suggest that Brd4 is recruited to osteoblast-specific genes and may cooperate with bone-related transcription factors to promote osteoblast lineage commitment and maturation.
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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.